促卵泡激素抑制的自噬通过p62-Nrf2途径保护山羊支持细胞免受氧化应激。
FSH-inhibited autophagy protects against oxidative stress in goat Sertoli cells through p62-Nrf2 pathway.
作者信息
Xi Huaming, Hu Zhangtao, Han Shuaiqi, Liu Xinyu, Wang Liqiang, Hu Jianhong
机构信息
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, 712100, People's Republic of China; Key Laboratory of Applied Technology on Green-Eco-Healthy Animal Husbandry of Zhejiang Province, Zhejiang Provincial Engineering Laboratory for Animal Health Inspection & Internet Technology, Zhejiang International Science and Technology Cooperation Base for Veterinary Medicine and Health Management, China-Australia Joint Laboratory for Animal Health Big Data Analytics, College of Animal Science and Technology & College of Veterinary Medicine of Zhejiang A&F University, Hangzhou, 311300, People's Republic of China.
Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest Agriculture and Forestry University, Yangling, Shaanxi, 712100, People's Republic of China.
出版信息
Theriogenology. 2023 Jan 1;195:103-114. doi: 10.1016/j.theriogenology.2022.10.022. Epub 2022 Oct 21.
Oxidative stress is a common cause of male infertility. Sertoli cells are one of the target cells of oxidative injury, which leads to impaired testicular function. Follicle-stimulating hormone (FSH) is critical in Sertoli cell function. However, the role of FSH in the response of goat Sertoli cells to HO-induced oxidative stress has not been studied yet. To investigate this response, we established an oxidative stress model using goat Sertoli cells. FSH pretreatment significantly enhanced the decreased cell viability (p < 0.05) caused by oxidative injury and inhibited autophagic flux. FSH significantly increased p62 mRNA and protein levels (p < 0.01). Further investigations revealed that FSH also increased the expression level and nuclear translocation of Nrf2 in Sertoli cells (p < 0.01), which resulted in increased antioxidant enzyme activity (p < 0.05). In contrast, treatment with siNrf2 and sip62 abolished this protective effect of FSH. These findings suggest that FSH protects Sertoli cells against oxidative stress via the p62-Nrf2 pathway, and that p62 accumulation maintains persistent activation of Nrf2. Thus, p62 and Nrf2 are required for FSH-mediated protective role in HO-induced Sertoli cell injury. The findings reveal new mechanisms by which FSH protects against oxidative injury in goat Sertoli cells.
氧化应激是男性不育的常见原因。支持细胞是氧化损伤的靶细胞之一，这会导致睾丸功能受损。促卵泡激素（FSH）对支持细胞功能至关重要。然而，FSH在山羊支持细胞对过氧化氢（HO）诱导的氧化应激反应中的作用尚未得到研究。为了研究这种反应，我们利用山羊支持细胞建立了氧化应激模型。FSH预处理显著增强了氧化损伤引起的细胞活力下降（p<0.05），并抑制了自噬流。FSH显著增加了p62的mRNA和蛋白水平（p<0.01）。进一步研究表明，FSH还增加了支持细胞中Nrf2的表达水平和核转位（p<0.01），这导致抗氧化酶活性增加（p<0.05）。相反，用siNrf2和sip62处理消除了FSH的这种保护作用。这些发现表明，FSH通过p62-Nrf2途径保护支持细胞免受氧化应激，并且p62的积累维持了Nrf2的持续激活。因此，p62和Nrf2是FSH介导的对HO诱导的支持细胞损伤的保护作用所必需的。这些发现揭示了FSH保护山羊支持细胞免受氧化损伤的新机制。
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