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Inhibition of SIRT1 Alters Apoptotic and Sex Related Genes in Zebrafish (Danio rerio)
Örebro University, School of Science and Technology.
2014 (English)Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
Abstract [en]

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.

Abstract [sv]

Sirtuin 1 (SIRT1) är ett nicotinamide adenine dinucleotide-beroende deacetylas som tillhör proteinfamiljen sirtuiner. Proteinet har kopplats till både cancer genom sin effekt på p53 och åldersrelaterade sjukdomar genom sin effekt på PPAR-γ (Peroxisome Proliferator-Activated Receptor gamma). Ny data har även visat ett samband mellan SIRT1, manlig fertilitet och spermatogenes. Då mekanismen för sexdifferentiering hos zebrafiskar fortfarande inte är väl förstådd är sirt1 genen ett intressant mål att studera för att öka förståelsen kring detta ämne. Zebrafiskar av olika ålder exponerades för olika koncentrationer av EX-527 för att inhibera SIRT1 proteinet. Därefter gjordes qRT-PCR analys av apoptotiska och sexrelaterade gener. Både apoptotiska och sexrelaterade geners utrycksnivåer påverkades av exponeringen. Vilka gener som påverkades och hur, skiljde sig i de flesta fall både mellan koncentrationerna av EX-527 som de utsatts för, och mellan åldern på zebrafiskarna. Den han-specifika genen sox9a (sex determining region Y box 9A) var nedreglerad i båda undersökta EX-527 koncentrationerna hos både zebrafiskar i larvstadiet och hos juvenila. Exponeringen av EX-527 gav ingen signifikant skillnad av könskvoten. Vidare studier krävs för att kunna beskriva signalvägen för SIRT1 genreglering i zebrafiskar.

Place, publisher, year, edition, pages
2014. , 29 p.
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:oru:diva-34760OAI: oai:DiVA.org:oru-34760DiVA: diva2:712770
Subject / course
Biology
Supervisors
Examiners
Available from: 2014-04-16 Created: 2014-04-16 Last updated: 2017-10-17Bibliographically approved

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CiteExportLink to record
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