Sirtuin 3-mediated deacetylation of superoxide dismutase 2 ameliorates sodium fluoride-induced mitochondrial dysfunction in porcine oocytes
Sirtuin 3-mediated deacetylation of superoxide dismutase 2 ameliorates sodium fluoride-induced mitochondrial dysfunction in porcine oocytes
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DOI：
10.1016/j.scitotenv.2023.168306
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发表时间：
2023-11-11
影响因子：
9.8
通讯作者：
Jin，Jun-Xue
中科院分区：
文献类型：
--
作者：
Qi，Xin-Yue;Yuan，Jin-Dong;Jin，Jun-Xue
氟化物对生殖细胞产生有害影响，增加妇女的不孕率。然而，氟在卵母细胞中引起的发育异常背后的确切机制仍然知之甚少。本研究通过添加50 μg/mL氟化钠（NaF）建立了卵母细胞线粒体损伤模型。然后，我们研究了和厚朴酚在预防NaF引起的线粒体缺陷中的作用，并研究了和厚朴酚保护卵母细胞的机制。研究结果表明，NaF增加了线粒体活性氧（mtROS）的水平，阻碍了线粒体功能，如线粒体膜电位的耗散，线粒体DNA拷贝数的异常表达，以及卵母细胞中mtDNA的损伤。用Mito-TEMPO清除线粒体ROS可减轻线粒体的氧化损伤，恢复卵母细胞的发育能力。超氧化物歧化酶2（SOD 2）乙酰化显着增加，而沉默调节蛋白3（SIRT 3）的表达下降，在氟化钠处理的卵母细胞。和厚朴酚的加入有助于通过SIRT 3使K122处的SOD 2脱乙酰化，从而去除过量的mtROS并恢复线粒体功能。因此，SIRT 3/SOD 2通路有助于和诺明减轻氟化物诱导的线粒体功能障碍。总的来说，和诺碱通过控制线粒体ROS和线粒体功能改善了NaF引起的线粒体损伤，其中SIRT 3/SOD 2途径具有重要功能。这些研究结果表明，honokaline作为一个潜在的治疗策略NaF诱导的卵母细胞发育和线粒体缺陷。
Fluoride exerts detrimental effects on germ cells and increases the infertility rate in women. Nevertheless, the precise mechanisms behind the developmental abnormalities caused by fluoride in oocytes remain poorly comprehended. The current study, we established mitochondrial damage model in oocytesvia50 μg/mL sodium fluoride (NaF) supplementation. We then examined the effects of honokiol in preventing mitochondrial deficits caused by NaF and investigated the mechanisms through which honokiol protects oocytes. The findings investigated that NaF increased levels of mitochondrial reactive oxygen species (mtROS) and hindered mitochondrial function, as evidenced by the dissipation of mitochondrial membrane potential, abnormal expression of mitochondrial DNA copy numbers, and mtDNA harm in oocytes. mtROS scavenging using Mito-TEMPO alleviated oxidative damage in mitochondria and restored the oocyte developmental competence. Superoxide dismutase 2 (SOD2) acetylation was significantly increased, whereas sirtuin 3 (SIRT3) expression was decreased in NaF-treated oocytes. The addition of honokiol helped in the deacetylation of SOD2 at K122 through SIRT3, resulting in the removal of excessive mtROS and the recovery of mitochondrial function. Therefore, SIRT3/SOD2 pathway aids honokiol in mitigating fluoride-induced mitochondrial dysfunction. Overall, honokiol improved the mitochondrial harm caused by NaF by controlling mtROS and mitochondrial function, with the SIRT3/SOD2 pathway having an important function. These findings suggest honokiol as a potential therapeutic strategy for NaF-induced oocyte development and mitochondrial deficits.