Inhibition of SIRT1 Alters Apoptotic and Sex Related Genes in Zebrafish (Danio rerio)

Abstract: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide - dependent deacetylase that belongs to the sirtuin protein family. The protein has been linked to both cancer through its effect on p53 and age related illnesses through its effect on peroxisome proliferator-activated receptor gamma (PPAR-γ). Recent data have shown a correlation between SIRT1, male fertility and spermatogenesis. Because the mechanism of sex differentiation in zebrafish is still not wellunderstood the sirt1 gene is an attractive target to study in order to improve our understanding of this topic. Zebrafish of different age were exposed to various concentrations of EX-527 toinhibit the SIRT1 protein. This was followed by qRT-PCR analysis of apoptotic and sex-related genes. Both apoptotic and sex-related gene expression levels were affected by the exposure. There were differences in genes that were affected, both between the concentrations of EX-527, and between the ages of the exposed zebrafish. The male- specific gene sexdetermining region Y box 9A (sox9a) was down-regulated at both studied EX-527 concentrations in both zebrafish larvae and juveniles. The exposure of the EX-527 resulted in no significant difference in sex-ratio. Further studies are required to describe the pathway for SIRT1 gene regulation in zebrafish.