Glutathionylation: a regulatory role of glutathione in physiological processes

  • Kristina Dominko Institute Rudjer Bošković, Zagreb, Croatia
  • Domagoj Đikić Department of Animal Physiology, Faculty of Science, Univefrsity of Zagreb
Keywords: epigenetics, GLUTATHIONYLATION, GSH, TRANSCRIPTIONAL FACTORS, GSSG, IMMUNITY, immunity, transcriptional factors

Abstract

Glutathione (γ-glutamyl-cysteinyl-glycine) is an intracellular thiol molecule and a potent antioxidant that participates in the toxic metabolism phase II biotransformation of xenobiotics. It can bind to a variety of proteins in a process known as glutathionylation. Protein glutathionylation is now recognised as one of important posttranslational regulatory mechanisms in cell and tissue physiology. Direct and indirect regulatory roles in physiological processes include glutathionylation of major transcriptional factors, eicosanoids, cytokines, and nitric oxide (NO). This review looks into these regulatory mechanisms through examples of glutathione regulation in apoptosis, vascularisation, metabolic processes, mitochondrial integrity, immune system, and neural physiology. The focus is on the physiological roles of glutathione beyond biotransformational metabolism.

Author Biography

Domagoj Đikić, Department of Animal Physiology, Faculty of Science, Univefrsity of Zagreb

Associated professor

Department of Animal Physiology

Faculty of Science

University of Zagreb

References

REFERENCES:

Josephy PD. Genetic variations ih human glutathione transferase enzymes: significance for pharmacology and toxicology. Hum Genomics Proteomics 2010;2010:876940. doi: 10.4061/2010/876940

Wu D, Meydani SN, Sastre J, Hayek M, Meydani M. In vitro glutathione supplementation enhances interleukin-2 production and mitogenic response of peripheral blood mononuclear cells from young and old subjects. J Nutr 1994;124:655-663. PMID: 8169657.

Espinosa-Diez C, Miguel V, Mennerich D, Kietzmann T, Sánchez-Pérez P, Cadenas S, Lamas S. Antioxidant responses and cellular adjustments to oxidative stress. Redox Biol 2015;6:183-97. doi: 10.1016/j.redox.2015.07.008 Fang YZ, Yang S, Wu G. Free radicals, antioxidants and nutrition. Nutrition 2002;18:872– 879. PMID: 12361782.

Lu L, Pandey AK, Houseal MT, Mulligan MK. The genetic architecture of murine glutathione transferases. PLoS ONE 2016;11(2), art. no. e0148230. doi: 10.1371/journal.pone.0148230

Axarli I, Muleta AW, Chronopoulou EG, Papageorgiou AC, Labrou NE. Directed evolution of glutathione transferases towards a selective glutathione-binding site and improved oxidative stability. Biochim Biophys Acta 2017;1861(1 Pt A):3416-3428. doi: 10.1016/j.bbagen.2016.09.004.

Fernández-Checa JC. Redox regulation and signaling lipids in mitochondrial apoptosis. Biochem Biophys Res Commun 2003;304:471-479. PMID:12729581. doi:10.1016/S0006-291X(03)00619-3

Perricone C, De Carolis C, Perricone R. Glutathione: a key player in autoimmunity. Autoimmun Rev2009;8:697-701. doi:10.1016/j.autrev.2009.02.020

Brigelius-Flohé R, Flohé L. Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors. Antioxid Redox Signal 2011;15(8):2335–2381. doi: 10.1089/ars.2010.3534

Short JD, Downs K, Tavakoli S, Asmis R. Protein thiol redox signaling in monocytes and macrophages. Antioxidants and Redox Signaling 2016;25(15):816-835. doi: 10.1089/ars.2016.6697

Oršolić N, Gajski G, Garaj-Vrhovac V, Dikić D, Prskalo ZŠ, Sirovina D.DNA-protective effects of quercetin or naringenin in alloxan-induced diabetic mice. Eur J Pharmacol. 2011 656(1-3):110-8. doi: 10.1016/j.ejphar.2011.01.021.

Oršolić N, Goluža E, Dikić D, Lisičić D, Sašilo K, Rođak E, Jeleč Z, Lazarus MV, Orct T. Role of flavonoids on oxidative stress and mineral contents in the retinoic acid-induced bone loss model of rat. Eur J Nutr. 2014 53(5):1217-27. doi: 10.1007/s00394-013-0622-7.

Oršolić N, Skurić J, Dikić D, Stanić G.Inhibitory effect of a propolis on di-n-propyl disulfide or n-hexyl salycilate-induced skin irritation, oxidative stress and inflammatory responses in mice. Fitoterapia. 2014 Mar;93:18-30. doi: 10.1016/j.fitote.2013.12.007.

Brzović-Šarić V, Landeka I, Šarić B, Barberić M, Andrijašević L, Cerovski B, Oršolić N, Đikić D. Levels of selected oxidative stress markers in the vitreous and serum of diabetic retinopathy patients. Mol Vis. 2015;21:649-64. eCollection 2015.

Montero D, Tachibana C, Rahr Winther J, Appenzeller-Herzog C. Intracellular glutathione pools are heterogeneously concentrated. Redox Biol 2013;1:508-13. doi: 10.1016/j.redox.2013.10.005

Voehringer DW, McConkey DJ, McDonnell TJ, Brisbay S, Meyn RE. Bcl-2 expression causes redistribution of glutathione to the nucleus. Proc Natl Acad Sci USA 1998;95(6):2956–2960. PMID:9501197

Pastore A, Piemonte F. S-glutathionylation signaling in cell biology: progress and prospects. Eur J Pharm Sci 2012;46:279-292. doi: 10.1016/j.ejps.2012.03.010.

Yang PM, Wu ZZ, Zhang YQ, Wung BS. Lycopene inhibits ICAM-1 expression and NF-κB activation by Nrf2-regulated cell redox state in human retinal pigment epithelial cells. Life Sci 2016;155:94-101. doi: 10.1016/j.lfs.2016.05.006

Tiao M-M, Lin T-K, Wang P-W, Chen J-B, Liou C-W. The role of mitochondria in cholestatic liver injury. Chang Gung Med J 2009;32:346-353. PMID: 19664341.

Allen EMG, Mieyal JJ. Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins. Antioxidants and Redox Signaling 2012;17(12):1748-1763. doi: 10.1089/ars.2012.4644

Meister A. Glutathione metabolism and its selective modification. J Biol Chem 1988;263:17205-17208. PMID: 3053703

Mårtensson J, Jain A, Stole E, Frayer W, Auld PA, Meister A. Inhibition of glutathione synthesis in the newborn rat: A model for endogenously produced oxidative stress. Proc Natl Acad Sci USA 1991; 88:9360-9364. doi:10.1073/pnas.88.20.9360

Lash LH. Role of glutathione transport processes in kidney function. Toxicol Appl Pharm 2005;204:329-342. doi:10.1016/j.taap.2004.10.004

Wu G, Fang YZ, Yang S, Lupton JR, Turner ND. Glutathione metabolism and its implications for health. J Nutr 2004;134:489-492. PMID: 14988435.

Lu SC. Glutathione synthesis. Biochim Biophys Acta 2013;1830(5):3143-53. doi: 10.1016/j.bbagen.2012.09.008

Hansen JM, Harris C. Glutathione during embryonic development.Biochim Biophys Acta 2015;1850(8):1527-42. doi: 10.1016/j.bbagen.2014.12.001.

Pias EK, Aw TY. Apoptosis in mitotic competent undifferentiated cells in induced by cellular redox imbalance independent of reactive oxygen species. FASEB J 2002a;16:781-790. doi:10.1096/fj.01-0784com

Griendling KK, Sorescu D, Lassègue B, Ushio-Fukai M. Modulation of protein kinase activity and gene expression by reactive oxygen species and their role in vascular physiology and pathophysiology. Arterioscler Thromb Vasc Biol 2000;20:2175-2183. doi: 10.1161/01.ATV.20.10.2175.

Castro L, Freeman BA. Reactive oxygen species in human health and disease. Nutrition 2001;17:161-165. PMID: 11240347.

Chia AJL, Goldring CE, Kitteringham NR, Wong SQ, Morgan P, Park BK. Differential effect of covalent protein modification and glutathione depletion on the transcriptional response of Nrf2 and NF-κB. Biochem Pharmacol 2010; 80:410-421. doi:10.1016/j.bcp.2010.04.004

Zuo L, Zhou T, Pannell BK, Ziegler AC, Best TM. Biological and physiological role of reactive oxygen species - the good, the bad and the ugly. Acta Physiol (Oxf) 2015;214(3):329-348. doi: 10.1111/apha.12515

Mieyal JJ, Gallogly MM, Qanungo S, Sabens EA, Shelton MD. Molecular mechanisms and clinical implications of reversible protein S-glutathionylation. Antioxid Redox Signal 2008;10(11):1941-88. doi: 10.1089/ars.2008.2089

Ghezzi P. Protein glutathionylation in health and disease. Biochim Biophys Acta 2013;1830(5):3165-72. doi: 10.1016/j.bbagen.2013.02.009

Sies H. Glutathione and its role in cellular functions. Free Radic Biol Med 1999;27:916-921. PMID: 10569624.

Ault JG, Lawrence DA. Glutathione distribution in normal and oxidatively stressed cells. Exp Cell Res 2003;285:9-14. doi:10.1016/S0014-4827(03)00012-0

Tew KD, Townsend DM. Glutathione-S-transferases as determinants of cell survival and death. Antioxid Redox Signal 2012;17:1728-1737. doi:10.1089/ars.2012.4640.

Maiorino M, Bosello-Travain V, Cozza G, Miotto G, Roveri A, Toppo S, Zaccarin M, Ursini F. Understanding mammalian glutathione peroxidase 7 in the light of its homologs Free Radic Biol Med 2015;83:352-360. doi: 10.1016/j.freeradbiomed.2015.02.017

Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radic Biol Med 2016;95: 27-42. doi:10.1016/j.freeradbiomed.2016.02.028

Grek CL, Zhang J, Manevich Y, Townsend DM, Tew KD. Causes and consequences of cysteine s-glutathionylation. J Biol Chem 2013;288(37):26497-504. doi: 10.1074/jbc.R113.461368

Hughes MM, McGettrick AF, O'Neill LA. 2017. Glutathione and Glutathione Transferase Omega 1 as Key Posttranslational Regulators in Macrophages.Microbiol Spectr. 5(1). doi: 10.1128/microbiolspec.MCHD-0044-2016.

Deponte, M. Glutathione catalysis and the reaction mechanisms of glutathione-dependent enzymes. Biochim Biophys Acta 2013;1830(5):3217-66. doi: 10.1016/j.bbagen.2012.09.018.

Mashamaite LN, Rohwer, JM, Pillay CS. The glutaredoxin mono- And di-thiol mechanisms for deglutathionylation are functionally equivalent: Implications for redox systems biology. Biosci Rep 2015;35(1). pii: e00173. doi: 10.1042/BSR20140157

Ercolani L, Scirè A, Galeazzi R, Massaccesi L, Cianfruglia L, Amici A, Piva F, Urbanelli L, Emiliani C, Principato G, Armeni T. A possible S-glutathionylation of specific proteins by glyoxalase II: An in vitro and in silico study. Cell Biochem Funct 2016;34(8):620-627. doi: 10.1002/cbf.3236. PMID: 27935136; DOI: 10.1002/cbf.3236

Harvey CJ, Thimmulappa RK, Singh A, Blake DJ, Ling G, Wakabayashi N, Fujii J, Myers A, Biswal S. Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med 2009;46:443-453. doi:10.1016/j.freeradbiomed.2008.10.040.

Lewerenz J, Hewett SJ, Huang Y, Lambros M, Gout PW, Kalivas PW, Massie A, Smolders I, Methner A, Pergande M, Smith SB, Ganapathy V, Maher P. The cystine/glutamate antiporter system xc - in health and disease: From molecular mechanisms to novel therapeutic opportunities. Antioxid Redox Signal 2013;18(5):522-55. doi: 10.1089/ars.2011.4391

Huang Y, Li W, Su ZY, Kong ANT. The complexity of the Nrf2 pathway: Beyond the antioxidant response. J Nutr Biochem 2015;26(12):1401-13. doi: 10.1016/j.jnutbio.2015.08.001

Bachhawat AK, Thakur A, Kaur J, Zulkifli M. 2013. Glutathione transporters. Biochim Biophys Acta.1830(5):3154-64. doi: 10.1016/j.bbagen.2012.11.018.

Meng Q, Peng Z, Chen L, Si J, Dong Z, Xia Y. Nuclear factor-κB modulates cellular glutathione and prevents oxidative stress in cancer cells. Cancer Lett 2010;299:45-53. doi:10.1016/j.canlet.2010.08.002.

Snyder NW, Golin-Bisello F, Gao Y, Blair IA, Freeman BA, Wendell SG. 15-Oxoeicosatetraenoic acid is a 15-hydroxyprostaglandin dehydrogenase-derived electrophilic mediator of inflammatory signaling pathways. Chem Biol Interact 2015;234:144-53. doi: 10.1016/j.cbi.2014.10.029

Reddy NM, Kleeberger SR, Yamamoto M, Kensler TW, Scollick C, Biswal S, Reddy SP. Genetic dissection of the Nrf2-dependent redox signaling-regulated transcriptional programs of cell proliferation and cytoprotection. Physiol Genomics 2007;32:74-81. doi:10.1152/physiolgenomics.00126.2007.

Fatehi-Hassanabad Z, Chan CB, Furman BL. Reactive oxygen species and endothelial function in diabetes. Eur J Pharmacol 2010;636:8-17. doi:10.1016/j.ejphar.2010.03.048

Schäfer M, Dütsch S, auf dem Keller U, Navid F, Schwarz A, Johnson DA, Johnson JA, Werner S. Nrf2 establishes a glutathione-mediated gradient of UVB cytoprotection in the epidermis. Gene Dev 2010;24:1045-1058. doi:10.1101/gad.568810.

Queisser N, Oteiza, PI, Link S, Hey V, Stopper H, Schupp N. Aldosterone activates transcription factor Nrf2 in kidney cells both in vitro and in vivo. Antioxid Redox Signal 2014;21(15):2126-42. doi: 10.1089/ars.2013.5565

Cebula M, Schmidt EE, Arnér ESJ. TrxR1 as a potent regulator of the Nrf2-Keap1 response system. Antioxid Redox Signal 2015;23(10):823-53. doi: 10.1089/ars.2015.6378

Radak Z, Zhao Z, Koltai E, Ohno H, Atalay M. Oxygen consumption and usage during physical exercise: the balance between oxidative stress and ROS-dependent adaptive signaling. Antioxid Redox Signal 2013;18(10):1208-46. doi: 10.1089/ars.2011.4498.

Carvalho AN, Marques C, Guedes RC, Castro-Caldas M, Rodrigues E, Van Horssen J, Gama MJ. S-Glutathionylation of Keap1: A new role for glutathione S-transferase pi in neuronal protection. FEBS Letters 2016;590(10):1455-1466. doi: 10.1002/1873-3468.12177

Lim J, Nakamura BN, Mohar I, Kavanagh TJ, Luderer U. Glutamate cysteine ligase modifier subunit (Gclm) null mice have increased ovarian oxidative stress and accelerated age-related ovarian failure. Endocrinology 2015;156(9):3329–3343. doi: 10.1210/en.2015-1206; PMCID: PMC4541624

Tomasi ML, Ryoo M, Yang H, Iglesias Ara A, Ko KS, Lu SC. Molecular mechanisms of lipopolysaccharide-mediated inhibition of glutathione synthesis in mice. Free Radic Biol Med 2014;68:148-158. doi:

Peng Z, Geh E, Chen L, Meng Q, Fan Y, Sartor M, Shertzer HG, Liu Z-G, Puga A, Xia Y. Inhibitor of κB kinase β regulates homeostasis by controlling the constitutive levels of glutathione. Mol Pharmacol 2010;77:784-792. doi: 10.1124/mol.109.061424

Li W, Busu C, Circu ML, Aw TY Glutathione in cerebral microvascular endothelial biology and pathobiology: implication for brain homeostasis. Int J Cell Biol 2012;1-14. ID 43497, 1DOI:10.1155/2012/434971. doi:

Ferguson G, Bridge W. Glutamate cysteine ligase and the age-related decline in cellular glutathione: The therapeutic potential of γ-glutamylcysteine Arch Biochem Biophys 2016;593:12-23. doi: 10.1016/j.abb.2016.01.01

Staal FJT, Roederer M, Herzenberg LA, Herzenberg LA. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. proc Natl Acad Sci USA 1990;87:9943-9947. PMID: 2263644.

Galter D, Mihm S, Dröge W. Distinct effects of glutathione disulphide on the nuclear transcription factor kappa B and the activator protein-1. Eur J Biochem 1994;221:639-648. doi: 10.1111/j.1432-1033.1994.tb18776.x

Pinkus R, Weiner LM, Daniel V. Role of oxidants and antioxidants in the induction of AP-1, NF-kappaB, and glutathione S-transferase gene expression. J Biol Chem 1996;7;271(23):13422-13429. PMID:8662787

Luo Y, Hattori A, Munoz J, Qin Z-H, Roth GS. Intrastriatal dopamine injection induced apoptosis through oxidation-involved activation of transcription factors AP-1 and NF-kappaB in rats. Mol Pharmacol 1999; 56:254-264. PMID: 10419543

Rahman I, MacNee W. Regulation of redox glutathione levels and gene transcription in lung inflammation: therapeutic approaches. Free Radic Biol Med 2000;28:1405-1420. PMID: 10924859.

Rahman I. Regulation of nuclear factor-kappa B, activator protein-1, and glutathione levels by tumor necrosis factor-alpha and dexamethasone in alveolar epithelial cells. Biochem Pharmacol 2000;60:1041-1049. PMID: 11007940.

Grimble RF. The effects of sulfur amino acid intake on immune function in humans. J Nutr 2006;136(6 Suppl):1660S-1665S. PMID: 16702336.

Ji LL. Modulation of skeletal muscle antioxidant defense by exercise: role of redox signaling. Free Radic Biol Med 2008;44:142-152. doi:10.1016/j.freeradbiomed.2007.02.031

Demasi M, Netto LES, Silva GM, Hand A, de Oliveira CLP, Bicev RN, Gozzo F, Barros, MH, Leme JMM, Ohara E. Redox regulation of the proteasome via S-glutathionylation. Redox Biol 2013;2:44-51. doi: 10.1016/j.redox.2013.12.003.

Kil IS, Kim SY, Park J-W Glutathionylation regulates IkappaB. Biochem Biophys Res Commun 2008;373:169-173. doi:10.1016/j.bbrc.2008.06.007.

Watson WH, Yang X, Choi YE, Jones DP, Kehrer JP. Thioredoxin and its role in toxicology. Toxicol Sci 2004;78:3-14. doi: 10.1093/toxsci/kfh050

Avogaro A, Vigili de Kreutzenberg S Mechanism of endothelial dysfunction in obesity. Clin Chim Acta 2005;360:9-26. doi:10.1016/j.cccn.2005.04.020

Musiek ES, Milne GL, Mclaughlin B, Morrow JD. Cyclopentenone eicosanoids as mediators of neurodegeneration: a pathogenic mechanism of oxidative stress-mediated and cyclooxygenase-mediated neurotoxicity. Brain Pathol 2005;15:149-158. doi: 10.1111/j.1750-3639.2005.tb00512.x

Ghashghaeinia M, Toulany M, Saki M, Rodemann HP, Mrowietz U, Lang F, Wieder T. Potential roles of the NFκB and glutathione pathways in mature human erythrocytes. Cell Mol Biol Lett 2012;17:11-20. doi. 10.2478/s11658-011-0032-x

Griffith OW. Biologic and pharmacologic regulation of mammalian glutathione synthesis. Free Radic Biol Med 1999;27:922-935. doi:org/10.1016/S0891-5849(99)00176-8

Bossis G, Malnou CE, Farras R, Andermarcher E, Hipskind R, Rodriguez M, Schmidt D, Muller S, Jariel-Encontre I, Piechaczyk M Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation. Mol Cell Biol 2005;25:6964-6979. doi:10.1128/MCB.25.16.6964–6979.2005

Karihtala P, Soini Y. Reactive oxygen species and antioxidant mechanisms in human tissues and their relation to malignancies. APMIS 2007;115:81-103. doi: 10.1111/j.1600-0463.2007.apm_514.x

Monje P, Hernández-Losa J, Lyons RJ, Castellone MD, Gutkind JS. Regulation of the transcriptional activity of c-Fos by ERK. A novel role for the prolyl isomerase PIN1. J Biol Chem 2005;280:35081-35084. doi: 10.1074/jbc.C500353200

Rahman I. Regulation of glutathione in inflammation and chronic lung diseases. Mutat Res 2005;579:58-80. doi:10.1016/j.mrfmmm.2005.02.025

Lu CY, Yang YC, Li CC, Liu KL, Lii CK, Chen HW. Andrographolide inhibits TNFα-induced ICAM-1 expression via suppression of NADPH oxidase activation and induction of HO-1 and GCLM expression through the PI3K/Akt/Nrf2 and PI3K/Akt/AP-1 pathways in human endothelial cells Biochem Pharmacol 2014;91(1):40-50. doi: 10.1016/j.bcp.2014.06.024

Abate C, Patel L, Rauscher FJ3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science 1990;249:1157–1161.

Klatt P, Lamas S. Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem 2000;267:4928-4944. doi:: 10.1046/j.1432-1327.2000.01601.x

Madamanchi NR, Runge MS. Redox signaling in cardiovascular health and disease. Free Radic Biol Med 2013;0:473–501. doi: 10.1016/j.freeradbiomed.2013.04.001 PMCID: PMC3883979 NIHMSID: NIHMS487851

Owen CA. Proteinases and oxidants as targets in the treatment of chronic obstructive pulmonary disease. Proc Am Thorac Soc 2005;2:373-385. doi: 10.1513/pats.200504-029SR.

Pias EK, Aw TY. Early redox imbalance mediates hydroperoxide-induced apoptosis in mitotic competent undifferentiated PC-12 cells. Cell Death Differ 2002;9(9):1007-1016 doi:10.1038/sj.cdd.4401064.

Franco R, Cidlowski JA Apoptosis and glutathione. beyond an antioxidant. Cell Death Differ 2009; 16:1303-1314. doi:10.1038/cdd.2009.107.

Yamaguchi T, Katoh I, Kurata S. Azidothymidine causes functional and structural destruction of mitochondria, glutathione deficiency and HIV-1 promoter sensitization. Eur J Biochem 2002;269:2782-2788. PMID: 12047388.

Ahmadi-Ahstiani HR, Bakhshandi AK, Rahbar M, Mirzaei A, Malekpour A, Rastegar H. Glutathione, cell proliferation and differentiation. Afr J Biotechnol 2011;10:6348-6363. doi: 10.1007/s11418-011-0554-6.

Watanabe Y, Murdoch CE, Sano, S, Ido Y, Bachschmid MM, Cohen RA, Matsui R. Glutathione adducts induced by ischemia and deletion of glutaredoxin-1 stabilize HIF-1α and improve limb revascularization.Proc Natl Acad Sci USA 2016;113(21):6011-6016. doi: 10.1073/pnas.1524198113

Velu CS, Niture SK, Doneanu CE, Pattabiraman N, Srivenugopal KS. Human p53 is inhibited by glutathionylation of cysteines present in the proximal DNA-binding domain during oxidative stress. Biochemistry 2007;46(26):7765-7780. doi: 10.1021/bi700425y

Riscal R, Schrepfer E, Arena G, Cissé MY, Bellvert F, Heuillet M, Rambow F, Bonneil E, Sabourdy F, Vincent C, Ait-Arsa I, Levade T, Thibaut P, Marine J-C, Portais J-C, Sarry J-E, Le Cam L, Linares LK. Chromatin-Bound MDM2 Regulates Serine Metabolism and Redox Homeostasis Independently of p53. Mol Cell 2016;62(6):890-902. doi: 10.1016/j.molcel.2016.04.033

Esposito K, Nappo F, Marfella R, Giugliano G, Giugliano F, Ciotola M, Quagliaro L, Ceriello A, Giugliano D. Inflammatory cytokine concentrations are acutely increased by hyperglycemia in humans: role of oxidative stress. Circulation 2002;106:2067-2072. doi: 10.1161/01.CIR.0000034509.14906.AE

Hallenborg P, Petersen RK, Kouskoumvekaki I, Newman JW, Madsen L, Kristiansen K.The elusive endogenous adipogenic PPARγ agonists: Lining up the suspects.Prog Lipid Res 2016;61:149-62. doi: 10.1016/j.plipres.2015.11.002.

Polvani S, Tarocchi M, Galli A. PPARγ and Oxidative Stress: Con(β) Catenating NRF2 and FOXO.PPAR Res 2012;2012:641087. doi: 10.1155/2012/641087.

Frohnert BI, Long EK, Hahn WS, Bernlohr DA. Glutathionylated Lipid Aldehydes Are Products of Adipocyte Oxidative Stress and Activators of Macrophage Inflammation. Diabetes 2014;63(1):89-100. doi: 10.2337/db13-0777

Prasad A, Andrews NP, Padder FA, Husain M, Quyyumi AA. Glutathione reverses endothelial dysfunction and improves nitric oxide bioavailability. J Am Coll Cardiol 1999;34:507-514. PMID: 10440166.

Mariappan N, Elks CM, Sriramula S, Guggilam A, Liu Z, Borkhsenious O, Francis J. NF-κB-induced oxidative stress contributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc Res 2009;85:473-483. doi:10.1093/cvr/cvp305.

Moran LK, Gutteridge JM, Quinlan GJ. Thiols in cellular redox signalling and control. Curr Med Chem 2001;8:763-772. PMID: 11375748

Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González A, Esquivel-Chirino C, Durante-Montiel I, Sánchez-Rivera G, Valadez-Vega C, Morales-González JA. Inflammation, oxidative stress, and obesity. Int J Mol Sci 2011;12(5):3117-32. doi: 10.3390/ijms12053117

Landeka Jurčević I, Mirna Dora M, Guberović I, Petras M, Rimac Brnčić S, Đikić D. Wine lees as a novel functional bioactive compound in protection against oxidative stress and hyperlipidemia. Food Tech Biotech 2017. Advanced online. doi: 10.17113/ftb.55.01.17.4894

Oakley AJ. Glutathione transferases: new functions. Curr Opin Struct Biol 2005;15:716-723. doi: 10.1016/j.sbi.2005.10.005

Thorén S, Jakobsson P-J. Coordinate up- and down-regulation of glutathione-dependent prostaglandin E synthase and cyclooxygenase-2 in A549 cells. Eur J Biochem 2000;267:6428-6434. PMID: 11029586.

Samuelsson B, Morgenstern R, Jakobsson PJ. Membrane prostaglandin E synthase-1: a novel therapeutic target. Pharmacol Rev 2007;59(3):207-224 doi:10.1124/pr.59.3.1.

Kanaoka Y, Maekawa A, Penrose JF, Austen KF, Lam BK. Reduced zymosan-induced peritoneal vascular permeability and IgE-dependent passive cutaneous anaphylaxis in mice lacking leukotriene C4 synthase. J Biol Chem 2001;276:22608-22613. doi 10.1074/jbc.M103562200

Wang W, Ballatori N. Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev 1998;50:335-356. PMID: 9755286.

Korzekwa AJ, Bodek G, Bukowska J, Blitek A, Skarzynski DJ. Characterization of bovine immortalized luteal endothelial cells: action of cytokines on production and content of arachidonic acid metabolites. Reprod Biol Endocrinol 2011;9:27-37. doi: 0.1186/1477-7827-9-27

Black AT, Gordon MK, Heck DE, Gallo MA, Laskin DL, Laskin JD. UVB light regulates expression of antioxidants and inflammatory mediators in human corneal epithelial cells. Biochem Pharmacol 2011;81:873-880. doi:10.1016/j.bcp.2011.01.014

Cornejo-García JA, Perkins JR, Jurado-Escobar R, García-Martín E, Agúndez JA, Viguera E, Pérez-Sánchez N, Blanca-López N. Pharmacogenomics of Prostaglandin and Leukotriene Receptors. Front Pharmacol 2016;7:316. doi: 10.3389/fphar.2016.00316 PMID: 27708579 PMCID: PMC5030812

Finkensieper A, Kieser S, Bekhite MM, Richter M, Mueller JP, Graebner R, Figulla H-R, Sauer H, Wartenberg M. The 5-lipoxygenase pathway regulates vasculogenesis in differentiating mouse embryonic stem cells. Cardiovasc Res 2010;86:37-44. doi:10.1093/cvr/cvp385

Niegowski D, Kleinschmidt T, Ahmad S, Qureshi AA, Mårback M, Rinaldo-Matthis A, Haeggström JZ. Structure and Inhibition of Mouse Leukotriene C4 Synthase. PLoS One 2014;9(5):e96763. doi: 10.1371/journal.pone.0096763

Martinez Molina D, Wetterholm A, Kohl A, McCarthy AA, Niegowski D, Ohlson E, Hammarberg T, Eshaghi S, Haeggström JZ, Nordlund P. Structural basis for synthesis of inflammatory mediators by human leukotriene C4 synthase. Nature 2007;448:613-616. doi:10.1038/nature06009

Elsas PX, Queto T, Mendonça-Sales SC, Elsas MI, Kanaoka Y, Lam BK. Cysteinyl leukotrienes mediate the enhancing effects of indomethacin and aspirin on eosinophil production in murine bone marrow cultures. Br J Pharmacol 2008;153:528-535. doi:10.1038/sj.bjp.0707586

Rouzer CA, Scott WA, Griffith OW, Hamill AL, Cohn ZA. Depletion of glutathione selectively inhibits synthesis of leukotriene C by macrophages. Proc Natl Acad Sci USA 1981;78:2532-2536. PMID:6113592

Samuelsson B. Arachidonic acid metabolism: role in inflammation. Z Rheumatol 1991;50:3-6. PMID: 1907059

Brock TG. Regulating leukotriene synthesis: the role of nuclear 5-lipoxygenase. J Cell Biochem 2005;96:1203-1211. doi: 10.1002/jcb.20662

Rinaldo-Matthis A, Wetterholm A, Martinez Molina D, Holm J, Niegowski D, Ohlson E, Nordlund P, Morgenstern R, Haeggström JZ. Arginine 104 is a key catalytic residue in leukotriene C4 synthase. J Biol Chem 2010;285:40771-40776. doi:10.1074/jbc.M110.105940

Penrose JF, Spector J, Baldasaro M, Xu K, Boyce, Arm JP, Austen KF, Lam BK. Molecular cloning of the gene for human leukotriene C4 synthase. J Biol Chem 1996;271:11356-11361. doi: 10.1074/jbc.271.19.11356

Penrose JF. LTC4 synthase. Enzymology, biochemistry, and molecular characterization. Clin Rev Allergy Immunol 1999;17:133-152. doi: 10.1007/BF02737601

Ago H, Kanaoka Y, Irikura D, Lam BK, Shimamura T, Austen KF, Miyano M Crystal structure of a human membrane protein involved in cysteinyl leukotriene biosynthesis. Nature 2007;448:609-612. PMID: 17632548.

Seidegård J, Ekström G. The role of human glutathione transferases and epoxide hydrolases in the metabolism of xenobiotics. Environ Health Perspect 1997;105:791-799. PMID: 9255563

Murakami M, Austen KF, Bingham CO 3rd, Friend DS, Penrose JF, Arm JP. Interleukin-3 regulates development of the 5-lipoxygenase/leukotriene c4 synthase pathway in mouse mast cells. J Biol Chem 1995;270:22653-22656. doi:10.1074/jbc.270.39.22653

Lam BK, Austen KF. Leukotriene C4 synthase: a pivotal enzyme in the biosynthesis of the cysteinyl leukotrienes. Am J Respir Crit Care Med 2000;161:16-19. PMID: 10673220.

Sanak M, Sampson AP. Biosynthesis of cysteinyl-leucotrienes in aspirin-intolerant asthma. Clin Exp Allergy 1999;29:306-313. doi: 10.1046/j.1365-2222.1999.00443.x

Mayatepek E. Leukotriene C4 synthesis deficiency: a member of a probably underdiagnosed new group of neurometabolic diseases. Eur J Pediatr 2000;158:811-818. doi:10.1007/s004310000601

Christmas P, Weber BM, McKee M, Brown D, Soberman RJ. Membrane localization and topology of leukotriene C4 synthase. J Biol Chem 2002;277:28902-28908. doi: 10.1074/jbc.M203074200

Sakamoto H, Imai H, Nakagawa Y. Involvement of phospholipid hydroperoxide glutathione peroxidase in the modulation of prostaglandin D2 synthesis. J Biol Chem 2000;275:40028-40035. doi: 10.1074/jbc.M003191200.

Yamagata K, Matsumura K, Inoue W, Shiraki T, Suzuki K, Yasuda S, Sugiura H, Cao C, Watanabe Y, Kobayashi S. Coexpression of microsomal-type prostaglandin E synthase with cyclooxygenase-2 in brain endothelial cells of rats during endotoxin-induced fever. J Neurosci 2001;21:2669-2677. PMID: 11306620.

Ishii T. Close teamwork between Nrf2 and peroxiredoxins 1 and 6 for the regulation of prostaglandin D2 and E2 production in macrophages in acute inflammation. Free Radic Biol Med 2015;88(Pt B):189-98. doi: 10.1016/j.freeradbiomed.2015.04.034

Murakami M, Naraba H, Tanioka T, Semmyo N, Nakatani Y, Kojima F, Ikeda T, Fueki M, Ueno A, Oh S, Kudo I. Regulation of prostaglandin E2 biosynthesis by inducible membrane-associated prostaglandin E2 synthase that acts in concert with cyclooxygenase-2. J Biol Chem 2000;275:32783-32792. doi:10.1074/jbc.M003505200

Blaine SA, Meyer AM, Hurteau G, Wick M, Hankin JA, Murphy RC, Dannenberg AJ, Geraci MW, Subbaramaiah K, Nemenoff RA. Targeted over-expression of mPGES-1 and elevated PGE2 production is not sufficient for lung tumorigenesis in mice. Carcinogenesis 2005;26:209-217. doi:10.1093/carcin/bgh302.

Jakobsson P-J, Thorén S, Morgenstern R, Samuelsson B. Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci USA 1999;96:7220-7225. PMID: 10377395

Thorén S, Weinander R, Saha S, Jegerschöld C, Petterson PL, Samuelsson B, Hebert H, Hamberg M, Morgenstern R, Jakobsson P-J. Human microsomal prostaglandin E synthase-1: purification, functional characterization, and projection structure determination. J Biol Chem 2003;278:22199-22209. doi: 10.1074/jbc.M303227200.

Gosset M, Berenbaum F, Levy A, Pigenet A, Thirion S, Saffar J-L, Jacques C. Prostaglandin E2 synthesis in cartilage explants under compression: mPGES-1 is mechanosensitive gene. Arthritis Res Ther 2006;8:135-148. doi:10.1186/ar2024

Schmidt-Krey I, Kanaoka Y, Mills DJ, Irikura D, Haase W, Lam BK, Austen KF, Kühlbrandt W. Human leukotriene C4 synthase at 4.5 å resolution in projection. Structure 2004;12:2009-2014. doi: 10.1016/j.str.2004.08.008

Kudo I, Murakami M Prostaglandin E synthase, a terminal enzyme for prostaglandin E2 biosynthesis. J Biochem Mol Biol 2005;38:633-638. PMID: 16336776

Sjögren T, Nord J, Ek M, Johansson P, Liu G, Geschwindnera S. Crystal structure of microsomal prostaglandin E2 synthase provides insight into diversity in the MAPEG superfamily. Proc Natl Acad Sci USA 2013;110(10):3806-3811. doi: 10.1073/pnas.1218504110

Gudis K, Tatsuguchi A, Wada K, Futagami S, Nagata K, Hiratsuka T, Shinji Y, Miyake K, Tsukui T, Fukuda Y, Sakamoto C. Microsomal prostaglandin E synthase (mPGES)-1, mPGES-2 and cytosolic PGES expression in human gastritis and gastric ulcer tissue. Lab Invest 2005; 85:225-236. doi:10.1038/labinvest.3700200

Takusagawa F. Microsomal prostaglandin E synthase type 2 (mPGES2;is a glutathione-dependent heme protein, and dithiothreitol dissociates the bound heme to produce active prostaglandin E2 synthase in vitro. J Biol Chem. 2013;5;288(14):10166-10175. doi: 10.1074/jbc.M112.418475.

Biswas SK, Rahman I. Environmental toxicity, redox signaling and lung inflammation: The role of glutathione. Mol Asp Med 2009;30:60-76. doi:10.1016/j.mam.2008.07.001

Aslani A, Ghobadi B. S. Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system Life Sci 2016;146:163-73. doi: 10.1016/j.lfs.2016.01.014.

Portal-Núñez S, Esbrit P, Alcaraz MJ, Largo R. Oxidative stress, autophagy, epigenetic changes and regulation by miRNAs as potential therapeutic targets in osteoarthritis. Biochem Pharmacol 2016;108:1-10. doi: 10.1016/j.bcp.2015.12.012

Haddad JJ, Safieh-Garabedian B, Saadé NE, Land SC. Thiol regulation of pro-inflammatory cytokines reveals a novel immunopharmacological potential of glutathione in the alveolar epithelium. J Pharmacol Exp Ther 2001;296:996-1005. PMID: 11181934

Villa P, Saccani A, Sica A, Ghezzi P. Glutathione protects mice from lethal sepsis by limiting inflammation and potentiating host defense. J Infect Dis 2002;185:1115-1120. PMID: 11930321.

Shelton MD, Mieyal JJ. Regulation by reversible S-glutathionylation: molecular targets implicated in inflammatory diseases. Mol Cells 2008;25(3):332-463. PMID:18483468

Jones JT, Qian X, van der Velden JL, Chia SB, McMillan DH, Flemer S, Hoffman SM, Lahue KG, Schneider RW, Nolin JD, Anathy V, van der Vliet A, Townsend DM, Tew KD, Janssen-Heininger YM. Glutathione S-transferase pi modulates NF-κB activation and pro-inflammatory responses in lung epithelial cells, Redox Biol 2016;8:375-82. doi: 10.1016/j.redox.2016.03.005

Chiou YS, Huang Q, Ho CT, Wang YJ, Pan MH. Directly interact with Keap1 and LPS is involved in the anti-inflammatory mechanisms of (-)-epicatechin-3-gallate in LPS-induced macrophages and endotoxemia. Free Radic Biol Med 2016;94:1-16. doi: 10.1016/j.freeradbiomed.2016.02.010

Peterson JD, Herzenberg LA, Vasquez K, Waltenbaugh C. Glutathione levels in antigen-presenting cells modulate Th1 versus Th2 response patterns. Proc Natl Acad Sci USA 1998;95:3071-3076. PMID: 9501217

Federico A, Morgillo F, Tuccillo C, Ciardiello F, Loguercio C. Chronic inflammation and oxidative stress in human carcinogenesis. Int J Cancer 2007;121:2381-2386. doi: 10.1002/ijc.23192

Dröge W, Pottmeyer-Gerber C, Schmidt H, Nick S. Glutathione augments the activation of cytotoxic T lymphocytes in vivo. Immunobiology 1986;172:151-156. PMID:3490430

Dröge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc 2000;59:595-600. PMID: 11115795.

Hussain T, Tan B, Yin Y, Blachier F, Tossou MCB, Rahu N. Oxidative Stress and Inflammation: What Polyphenols Can Do for Us? Oxid Med Cell Longev 2016;2016:7432797 doi:10.1155/2016/7432797.

Hadzic T, Li L, Cheng N, Walsh SA, Spitz DR, Knudson CM. The role of low molecular weight thiols in T lymphocyte proliferation and IL-2 secretion. J Immunol 2005;175:7965-7972. PMID:16339532

Kwyer TA, Bounous SG, Sataloff RT. Implications of nutriceutical modulation of glutathione with cystine adn cysteine. In: Voice Science; editor:Sataloff R.T., Plural Publishing, San Diego Ca,2005. pp 125-147. ISBN 1-59756-000-6

Madondo MT, Quinn M, Plebanski M. Low dose cyclophosphamide: Mechanisms of T cell modulation. Cancer Treat Rev 2016;42:3-9. doi: 10.1016/j.ctrv.2015.11.005

Fratelli M, Demol H, Puype M, Casagrande S, Eberini I, Salmona M, Bonetto V, Mengozzi M, Duffieux F, Miclet E, Bachi A, Vandekerckhove J, Gianazza E, Ghezzi P. Identification by redox proteomics of glutathionylated proteins in oxidatively stressed human T lymphocytes. Proc Natl Acad Sci USA 2002;99:3505-3510. doi:10.1073/pnas.052592699.

Sikalidis, A.K. Amino Acids and Immune Response: A Role for Cysteine, Glutamine, Phenylalanine, Tryptophan and Arginine in T-cell Function and Cancer? (2015) Pathol Oncol Res 2015;21(1):9-17. doi: 10.1007/s12253-014-9860-0

Suthanthiran M, Anderson ME, Sharma VK, Meister A. Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc Natl Acad Sci USA 1990;87:3343-3347. PMID: 1970635.

Aukrust P, Svardal AM, Müller F, Lunden B, Berge RK, Ueland PM, Frøland SS. Increased levels of Oxidized glutathione in CD4+ lymphocytes associated with disturbed intracellular redox balance in human immunodeficiency virus type 1 infection. Blood 1995;86:258-267. PMID: 7795231

Samikkannu T, Ranjith D, Rao KV, Atluri VS, Pimentel E, El-Hage N, Nair MP.HIV-1 gp120 and morphine induced oxidative stress: Role in cell cycle regulation. Front Microbiol 2015;6:614. doi: 10.3389/fmicb.2015.00614

Mukhopadhyay S, Hoidal JR, Mukherjee TK. Role of TNFalpha in pulmonary pathophysiology. Respir Res 2006;7:125-133. doi:10.1186/1465-9921-7-125

He Y, Jackman NA, Thorn TL, Vought VE, Hewett SJ. Interleukin-1β protects astrocytes against oxidant-induced injury via an NF-κB-dependent upregulation of glutathione synthesis.Glia. 2015;63(9):1568-80. doi: 10.1002/glia.22828.

Heales SJ, Bolaños JP. Impairment of brain mitochondrial function by reactive nitrogen species: the role of glutathione dictating susceptibility. Neurochem Int 2002;40:469-474. PMID: 11850103.

Yap LP, Sancheti H, Ybanez MD, Garcia J, Cadenas E, Han D. Determination of GSH and GSNO using HPLC with electrochemical detection. Methods Enzymol 2010;473:137-147. doi:10.1016/S0076-6879(10)73006-8.

Martínez-Ruiz A, Lamas S. Signalling by NO-induced protein S-nitrosylation and S-glutathionylation: convergences and divergences. Cardiovasc Res 2007;75:220-228. doi:10.1016/j.cardiores.2007.03.016

Calabrese V, Boyd-Kimball D, Scapagnini G, Butterfield DA. Nitric oxide and cellular response in brain ageing and neurodegenerative disorders: the roles of vitagenes. In vivo 2004;18:245-268. PMID: 15341181.

Li C-Q, Wogan GN. Nitric oxide as a modulator of apoptosis. Cancer Lett 2005;226:1-5. doi:10.1016/j.canlet.2004.10.021

Calabrese V, Cornelius C, Rizzarelli E, Owen JB, Dinkova-Kostova AT, Butterfield, DA. Nitric oxide in cell survival: A Janus molecule. Antioxid Redox Signal 2009;11:2717-39. doi: 10.1089/ARS.2009.2721.

Rauhala P, Andoh T, Chiueh CC. Neuroprotective properties of nitric oxide and S-nitrosoglutathione. Toxicol Appl Pharmacol 2005;207:91-95. doi:10.1016/j.taap.2005.02.028

Hudson VM. Rethinking cystic fibrosis pathology: the critical role of abnormal reduced glutathione (GSH) transport caused by CFTR mutation. Free Radic Biol Med 2001;30:1440-1461. doi: 10.1016/S0891-5849(01)00530-5.

Feelisch M. The use of nitric oxide donors in pharmacological studies. Naunyn-Schmiedebergs Arch Pharmacol 1998;358:113-122. doi: 10.1007/PL00005231

Hill BG, Bhatnagar A. Role of glutathiolation in preservation, restoration and regulation of protein function. IUBMB Life 2007;59:21-26. doi: 10.1080/15216540701196944

Khan M, Sakakima H, Dhammu TS, Shunmugavel A, Im Y-b, Gilg AG, Singh AK, Singh I. S-nitrosoglutathione reduces oxidative injury and promotes mechanisms neurorepair following traumatic brain injury in rats. J Neuroinflammation 2011;8:78-134. doi:10.1186/1742-2094-8-78

Broniowska, KA, Diers AR, Hogg N. S-Nitrosoglutathione. Biochim Biophys Acta. 2013;1830(5):3173-81. doi: 10.1016/j.bbagen.2013.02.004.

Del Rio LA. Peroxisomes as a cellular source of reactive nitrogen species signal molecules. Arch Biochem Biophys 2011;506:1-11. doi:10.1016/j.abb.2010.10.022

Guerra D, Ballard K, Truebridge I, Vierling E. S-nitrosation of conserved cysteines modulates activity and stability of S-nitrosoglutathione reductase (GSNOR). Biochemistry 2016;55(17):2452-64. doi: 10.1021/acs.biochem.5b01373

Nascimento NRF, Costa-e-Forti A, Peter AA, Fonteles MC. Free radical scavengers improve the impaired endothelium-dependent responses in aorta and kidneys of diabetic rabbits. Diabetes Res Clin Pract 2003;61:145-153. doi:10.1016/S0168-8227(03)00128-1.

Ganzarolli de Oliveira M. S-Nitrosothiols as Platforms for Topical Nitric Oxide Delivery. Basic Clin Pharmacol Toxicol 2016;119 Suppl 3:49-56. doi: 10.1111/bcpt.12588.

Duan S, Chen C. S-nitrosylation/denitrosylation and apoptosis of immune cells. Cell Mol Immunol 2007;4:353-358. PMID: 17976315.

Samuvel DJ, Shunmugavel A, Singh, AK, Singh I, Khan M. S-Nitrosoglutathione ameliorates acute renal dysfunction in a rat model of lipopolysaccharide-induced sepsis. J Pharm Pharmacol 2016;68(10):1310-9. doi: 10.1111/jphp.12608. Epub 2016

Wu W, Perrin-Sarrado C, Ming H, Lartaud I, Maincent P, Hu XM, Sapin-Minet A, Gaucher C.Polymer nanocomposites enhance S-nitrosoglutathione intestinal absorption and promote the formation of releasable nitric oxide stores in rat aorta.Nanomedicine 2016;12(7):1795-1803. doi: 10.1016/j.nano.2016.05.006.

Wu W, Gaucher C, Fries I, Hu XM, Maincent P, Sapin-Minet A. Polymer nanocomposite particles of S-nitrosoglutathione: A suitable formulation for protection and sustained oral delivery. Int J Pharm 2015;495(1):354-61. doi: 10.1016/j.ijpharm.2015.08.074.

Shah SU, Socha M, Fries I, Gibaud S. Synthesis of S-nitrosoglutathione-alginate for prolonged delivery of nitric oxide in intestines Drug Delivery 2016;23 (8):2927-2935. doi:

Murdoch CE, Bachschmid MM, Matsui R. Regulation of Neovascularization by S-glutathionylation via Wnt5a-sFlt-1 pathway Biochem Soc Trans 2014;42(6):1665–1670. doi: 10.1042/BST20140213. PMCID: PMC4934611.NIHMSID: NIHMS796286

Pimentel D, Haeussler DJ, Reiko Matsui, Burgoyne JR, Richard Alan Cohen RA, Bachschmid MM. Regulation of Cell Physiology and Pathology by protein S-Glutathionylation: lessons learned from the cardiovascular system. Antioxid Redox Signal 2012;16(6):524–542. doi: 10.1089/ars.2011.4336 PMCID: PMC3270052

Samarasinghe KT, Munkanatta Godage DN, Zhou Y, Ndombera FT, Weerapana E, Ahn YH. A clickable glutathione approach for identification of protein glutathionylation in response to glucose metabolism. Mol. BioSyst 2016;12:2471-2480 doi: 10.1039/C6MB00175K

Pal D, Sharma D, Kumar M, Sandur SK. Prediction of glutathionylation sites in proteins using minimal sequence information and their experimental validation. Free Radic Res 2016;50(9):1011-21. doi: 10.1080/10715762.2016.1216551.

Schwarzländer M, Dick TP, Meyer AJ, Morgan B. Dissecting redox biology using fluorescent protein sensors. Antioxid Redox Signal 2016;24(13):680-712. doi: 10.1089/ars.2015.6266

Mullen L, Seavill M, Hammouz R, Bottazzi B, Chan P, Vaudry D, Ghezzi P. Development of ‘Redox Arrays’ for identifying novel glutathionylated proteins in the secretome. Sci Reports 2015;5:14630.doi:10.1038/srep14630

Lu S, Fan SB, Yang B, Li YX, Meng JM, Wu L, Li P, Zhang K, Zhang MJ, Fu Y, Luo J, Sun RX, He SM, Dong MQ. Mapping native disulfide bonds at a proteome scale. Nature Meth 2015;12:329-331.doi:10.1038/nmeth.3283

Duan J, Kodali VK, Gaffrey MJ, et al. Quantitative Profiling of Protein S-Glutathionylation Reveals Redox-Dependent Regulation of Macrophage Function during Nanoparticle-Induced Oxidative Stress. ACS nano. 2016;10(1):524-538. doi:10.1021/acsnano.5b05524.

Hinchman CA, Ballatori N. Glutathione conjugation and conversion to mercapturic acids can occur as an intrahepatic process. J Toxicol Environ Health 1994;41:387-409. doi:10.1080/15287399409531852.

Wilson SM, Gleisten MP, Donohue TJ. Identification of proteins involved in formaldehyde metabolism by Rhodobacter sphaeroides. Microbiology 2008;154:296-305. doi: 10.1099/mic.0.2007/011346-0.

Zhang YT, Zheng QS, Pan J, Zheng RL. Oxidative damage of biomolecules in mouse liver induced by morphine and protected by antioxidants. Basic Clin Pharmacol Toxicol 2004;95:53-58. PMID: 15379780.

Lewerenz J, Maher P. Control of redox state and redox signaling by neural antioxidant systems. Antioxid Redox Signal 2011;14:1449-1465. doi:10.1089/ars.2010.3600.

Kryston TB, Georgiev AB, Pissis P. Role of oxidative stress and DNA damage in human carcinogenesis. Mutat Res 2011;711:193-201. doi:10.1016/j.mrfmmm.2010.12.016.

Forman HJ, Zhang H, Rinna A Glutathione: overview of its protective roles, measurement, and biosynthesis. Mol Aspects Med 2009;30:1-12. doi:10.1016/j.mam.2008.08.006.

Bogdanova A, Petrushanko IY, Hernansanz-Agustín P, Martínez-Ruiz A. Oxygen sensing" by Na,K-ATPase: These miraculous thiols. Front Physiol 2016;7:314. doi: 10.3389/fphys.2016.00314. eCollection 2016.

Gallogly MM, Mieyal JJ. Mechanisms of reversible protein glutathionylation in redox signaling and oxidative stress. Curr Opin Pharmacol 2007; 7:381-391. doi: 10.1016/j.coph.2007.06.003.

Day RM, Suzuki YJ. Cell proliferation, reactive oxygen species and cellular glutathione. Dose Response 2006; 3:425-442. doi: 10.2203/dose-response.003.03.010.

Sen CK, Packer L. Antioxidant and redox regulation of gene transcription. FASEB J 1996;10: 709-720. PMID: 8635688

Huh Y-J, Kim J-M, Kim H, Song H. Regulation of osteoclast differentiation by redox dependant modulation of nuclear import of transcription factors. Cell Death Differ 2006;13:1138-1146. doi:10.1038/sj.cdd.4401793

Jegerschöld C, Pawelzik S-C, Purhonen P, Bhakat P, Gheorghe KR, Gyobu N, Mitsuoka K, Morgenstern R, Jakobsson P-J, Hebert H. Structural basis for induced formation of the inflammatory mediator prostaglandin E2. Proc Natl Acad Sci USA 2008; 105:11110-11115. doi/10.1073/pnas.0802894105.

Armstrong JS, Whiteman M, Yang H, Jones DP, Sternberg Jr. P. Cysteine starvation activates the redox-dependent mitochondrial permeability transition in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 2004; 45:4183-4189. PMID: 15505073.

Vasdev S, Stuckless J. Role of methylglyoxal in essential hypertension. Int J Angiol 2010;19:58-65. PMID: 22477591

Published
2018-03-15
How to Cite
1.
Dominko K, Đikić D. Glutathionylation: a regulatory role of glutathione in physiological processes. Arh Hig Rada Toksikol [Internet]. 2018Mar.15 [cited 2024Mar.19];69(1). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/744
Section
Review