Abstract
An excess of oxidative stress (OS) may affect several physiological processes fundamental to reproduction. SIRT1, SIRT6 and SIRT7 are involved in protection stress systems caused by OS, and they can be activated by antioxidants such as celastrol or melatonin. In this study, we evaluate SIRT1, SIRT6 and SIRT7 gene expression in cultured human granulosa-lutein (hGL) cells in response to OS inductors (glucose or peroxynitrite) and/or antioxidants. Our results show that celastrol and melatonin improve cell survival in the presence and absence of OS inductors. In addition, melatonin induced SIRT1, SIRT6 and SIRT7 gene expression while celastrol only induced SIRT7 gene expression. This response was not altered by the addition of OS inductors. Our previous data for cultured hGL cells showed a dual role of celastrol as a free radical scavenger and as a protective agent by regulating gene expression. This study shows a direct effect of celastrol on SIRT7 gene expression. Melatonin may protect from OS in a receptor-mediated manner rather than as a scavenger. In conclusion, our results show increased hGL cells survival with melatonin or celastrol treatment under OS conditions, probably through the regulation of nuclear sirtuins’ gene expression.
Highlights
Oxidative stress (OS) or the imbalance between reactive oxygen species (ROS) and antioxidants, causes damage to proteins through aggregation and/or denaturation, lipid peroxidation and nucleotide changes in the DNA structure [1]
This research was performed to investigate the effects of celastrol and melatonin in preventing the impact of OS generated by glucose or peroxynitrite on cultured human granulosa-lutein (hGL) cells
We report that the addition of antioxidants to culture medium elicits an increase in the amount of high/medium level of 8-OHdG staining compared to the amount found in control cells, but in contrast, we found an increase in the total number of surviving cells (Figure 1B)
Summary
Oxidative stress (OS) or the imbalance between reactive oxygen species (ROS) and antioxidants, causes damage to proteins through aggregation and/or denaturation, lipid peroxidation and nucleotide changes in the DNA structure [1]. Sirtuins are a family of proteins with NAD+-dependent deacylase and/or ADP ribosyltransferase activity [4]. In mammals, this family includes seven sirtuins (SIRT1-SIRT7). That play an important role in many cellular biological processes such as transcriptional regulation, inflammatory response, oxidative stress, cell survival, DNA repair or energy metabolism [5]. Nuclear sirtuins include SIRT1, SIRT6 and SIRT7 [7]. OS is an important factor in inducing cell senescence because it leads to DNA damage or decreased telomerase activity [12]. The peroxisome proliferator activated receptor g (PPAR-g) is a non-histone protein target of SIRT1 and plays a role in the antioxidant stress system, inducing the
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