Sirtuins (SIRTs) are described as a family of nicotinamide adenine dinucleotide (NAD+)-dependent deacetylases and is able to catalyze post-translational modifications of proteins. It has been documented that, SIRTs respond to metabolic challenges, inflammation molecules, and oxidative stress. Many studies have linked SIRTs with longevity and having anti-aging activity. Our knowledge of SIRTs in reproduction has grown increasingly over the last few years. The majority of these research is carried out primarily on the effects on SIRT1 on female reproduction. It has been demonstarted that down-regulating SIRT1 trigers the reduction of ovarian reserve. Many research has demonstrated that, SIRT1 regulates proliferation and apoptosis in granulosa cells. Activity studies of SIRTs opened the discoveries of the functional aspects of different types of SIRTs in improving the overall quality of in vitro oocytes in humans and animal models. It has been documented that, SIRT1, SIRT2 and SIRT3 protect oocytes against postovulatory aging. The relationship between derangement of SIRT signaling and the imbalance of reactive oxygen species and antioxidant defenses in female reproductive organs has also been documented. The present review aims to put forward information on the mechanism and cellular role of SIRTs and give an update of sirtuin research in female reproduction under physiological and pathological conditions. The final goal of this work is to put forward the therapeutic potential of SIRTs in female infertility.
Keywords: Sirtuins; oocyte; ovary; reproduction; infertility
Sirtuinler (SIRT), proteinlerin translasyon sonrası modifikasyonlarını katalize eden bir nikotinamid adenin dinükleotid (NAD+) bağımlı deasetilaz ailesidir. Metabolik zorluklara, inflamatuar sinyallere veya hipoksik/oksidatif strese yanıt verirler ve yaşlanma ve uzun yaşam ile ilişkilidirler. SIRT'ler ile ilgili üreme alanındaki bilgimiz son birkaç yılda giderek artmıştır. Şimdiye kadar yapılan çalışmaların çoğu kadın üremesine dönük olup, SIRT1'e odaklanılmıştır. SIRT1 sentezinin azalması sonucunda ovaryan rezervin de azaldığı kanıtlanmıştır. SIRT1'in, granüloza hücre proliferasyonu ve apoptozunu düzenlediği de gösterilmiştir. SIRT'lerin biyokimyasal aktivitesinin ortaya çıkarılmasıyla SIRT1, SIRT2, SIRT3 ve SIRT6'nın insan ve hayvan modellerinde in vitro olarak geliştirilen oositler üzerindeki rollerinin keşfedilmesine yol açmıştır. Son zamanlarda SIRT1, SIRT2 ve SIRT3 oositin postovulatuar yaşlanmaya karşı koruyuculukları ortaya çıkmıştır. Ayrıca SIRT'lerin etkilediği sinyal yolaklarının düzensizleşmesi sonucu, kadın üreme organlarında reaktif oksijen türleri ve antioksidan savunma mekanizmalarındaki dengesizlik gösterilmiştir. Bu derleme, kadın üremesinde fizyolojik ve patolojik koşullar altında SIRT'lerin etki mekanizmaları ve hücresel rolü hakkında güncel bilgi aktarmayı amaçlamaktadır. Bu çalışmanın nihai amacı, kadın infertilitesinde tedavi amaçlı, SIRT'lerin potansiyel bir molekül olabileceği konusunu gündeme taşımaktır.
Anahtar Kelimeler: Sirtuinler; oosit; ovaryum; üreme; infertilite
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