1,4-dihydropyridine derivatives increase mRNA expression of Psma3, Psmb5, and Psmc6 in rats

  • Kristīne Dišlere Institute of Biology of the University of Latvia, Riga, Latvia
  • Evita Rostoka Faculty of Medicine, University of Latvia, Riga, Latvia
  • Egils Bisenieks Latvian Institute of Organic Synthesis, Riga, Latvia
  • Gunars Duburs Latvian Institute of Organic Synthesis, Riga, Latvia
  • Natalia Paramonova Institute of Biology of the University of Latvia, Riga, Latvia
  • Nikolajs Sjakste Faculty of Medicine, University of Latvia, Riga, Latvia
Keywords: Av-153-Ca, Av-153-Na, etcarbatone, gene expression, glutapyrone, impaired proteasomal functions, metcarbatone, pharmacological activities, proteasome subunits, styrylcarbatone, ubiquitin-proteasome system

Abstract

The ubiquitin-proteasome system modifies different cellular and protein functions. Its dysregulation may lead to disrupted proteostasis associated with multiple pathologies and aging. Pharmacological regulation of proteasome functions is already an important part of the treatment of several diseases. 1,4-dihydropyridine (1,4-DHP) derivatives possess different pharmacological activities, including antiaging and neuroprotective. The aim of this study was to investigate the effects of several 1,4-DHP derivatives on mRNA expression levels of proteasomal genes Psma3, Psmb5, and Psmc6 in several organs of rats. Rats were treated with metcarbatone, etcarbatone, glutapyrone, styrylcarbatone, AV-153-Na, or AV-153-Ca per os for three days. mRNA expression levels were determined with real-time polymerase chain reaction (PCR). For AV-153-Na and AV-153-Ca, we also determined the expression of the Psma6 gene. In the kidney, metcarbatone, etcarbatone, styrylcarbatone, and AV-153-Na increased the expression of all analysed genes. Glutapyrone increased the expression of Psmb5 and Psmc6 but did not affect the expression of Psma3. In the blood, glutapyrone increased Psmb5 expression. In the liver, AV-153-Na increased the expression of Psma6 and Psmc6 but lowered the expression of Psmb5, while AV-153-Ca only increased Psma6 expression. The ability of 1,4-DHP derivatives to increase the expression of proteasome subunit genes might hold a therapeutic potential in conditions associated with impaired proteasomal functions, but further research is needed.

Published
2021-06-07
How to Cite
1.
Dišlere K, Rostoka E, Bisenieks E, Duburs G, Paramonova N, Sjakste N. 1,4-dihydropyridine derivatives increase mRNA expression of Psma3, Psmb5, and Psmc6 in rats. Arh Hig Rada Toksikol [Internet]. 2021Jun.7 [cited 2021Jul.31];72(2). Available from: https://arhiv.imi.hr/index.php/arhiv/article/view/1280
Section
Original article

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