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Melatonin protects aged oocytes from depalmitoylation-mediated quality reduction by promoting PPT1 degradation and antioxidation
Redox Biology ( IF 10.7 ) Pub Date : 2025-01-21 , DOI: 10.1016/j.redox.2025.103510
Rujun Ma, Mengqi Xue, Feiyan Ge, Kadiliya Jueraitetibaike, Shanmeizi Zhao, Zhang Qian, Zhaowanyue He, Hong Zhang, Ting Tang, Chun Cao, Chuwei Li, Lu Zheng, Tongmin Xue, Jie Dong, Jun Jing, Jian Zhong, Jinzhao Ma, Yang Yang, Yadong Huang, Xie Ge, Bing Yao, Li Chen
Redox Biology ( IF 10.7 ) Pub Date : 2025-01-21 , DOI: 10.1016/j.redox.2025.103510
Rujun Ma, Mengqi Xue, Feiyan Ge, Kadiliya Jueraitetibaike, Shanmeizi Zhao, Zhang Qian, Zhaowanyue He, Hong Zhang, Ting Tang, Chun Cao, Chuwei Li, Lu Zheng, Tongmin Xue, Jie Dong, Jun Jing, Jian Zhong, Jinzhao Ma, Yang Yang, Yadong Huang, Xie Ge, Bing Yao, Li Chen
Oocyte aging is closely related to a decline in female fertility, accompanied by increased reactive oxygen species levels and changes in protein posttranslational modifications. However, the role of protein palmitoylation in oocyte aging has not been investigated. In the present study, a new association between redox and palmitoylation in aging oocytes was found. We found that the protein level of palmitoyl-protein thioesterase 1 (PPT1), a depalmitoylation enzyme, was increased in maternally aged mice oocytes and follicular fluid of aged (age >35 years) patients with decreased ovarian reserve (DOR). Elevated PPT1 led to decreased S-palmitoylation levels in oocytes, which impaired oocyte maturation and spindle formation. Tubulin was identified as a critical palmitoylated protein regulated by PPT1, whose palmitoylation was also decreased by advanced age, accompanied by abnormalities in membrane localization and microtubule polymerization. Melatonin was found to down-regulate excessive PPT1 and rescue PPT1-induced damage in mouse oocytes, not only by regulating oxidative stress, but also by binding with PPT1 to regulate its lysosomal degradation. In summary, our data demonstrate that PPT1 participates in oocyte aging by regulating tubulin palmitoylation, providing evidence that oxidative stress regulates protein palmitoylation and revealing a novel mechanism of oocyte aging.
中文翻译:
褪黑激素通过促进 PPT1 降解和抗氧化来保护老年卵母细胞免受去棕榈酰化介导的质量降低
卵母细胞衰老与女性生育能力下降密切相关,伴随着活性氧水平的增加和蛋白质翻译后修饰的变化。然而,蛋白质棕榈酰化在卵母细胞衰老中的作用尚未得到研究。在本研究中,发现了衰老卵母细胞中氧化还原和棕榈酰化之间的新关联。我们发现棕榈酰蛋白硫酯酶 1 (PPT1) 的蛋白质水平在卵巢储备 (DOR) 降低的老年 (年龄 >35 岁) 患者的母体小鼠卵母细胞和卵泡液中升高。PPT1 升高导致卵母细胞中 S-棕榈酰化水平降低,从而损害卵母细胞成熟和纺锤体形成。微管蛋白被鉴定为一种受 PPT1 调控的关键棕榈酰化蛋白,其棕榈酰化也随着年龄的增长而降低,并伴有膜定位和微管聚合异常。发现褪黑激素下调过量的 PPT1 并挽救 PPT1 诱导的小鼠卵母细胞损伤,不仅通过调节氧化应激,还通过与 PPT1 结合以调节其溶酶体降解。总之,我们的数据表明 PPT1 通过调节微管蛋白棕榈酰化参与卵母细胞衰老,提供了氧化应激调节蛋白质棕榈酰化的证据,并揭示了卵母细胞衰老的新机制。
更新日期:2025-01-21
中文翻译:
褪黑激素通过促进 PPT1 降解和抗氧化来保护老年卵母细胞免受去棕榈酰化介导的质量降低
卵母细胞衰老与女性生育能力下降密切相关,伴随着活性氧水平的增加和蛋白质翻译后修饰的变化。然而,蛋白质棕榈酰化在卵母细胞衰老中的作用尚未得到研究。在本研究中,发现了衰老卵母细胞中氧化还原和棕榈酰化之间的新关联。我们发现棕榈酰蛋白硫酯酶 1 (PPT1) 的蛋白质水平在卵巢储备 (DOR) 降低的老年 (年龄 >35 岁) 患者的母体小鼠卵母细胞和卵泡液中升高。PPT1 升高导致卵母细胞中 S-棕榈酰化水平降低,从而损害卵母细胞成熟和纺锤体形成。微管蛋白被鉴定为一种受 PPT1 调控的关键棕榈酰化蛋白,其棕榈酰化也随着年龄的增长而降低,并伴有膜定位和微管聚合异常。发现褪黑激素下调过量的 PPT1 并挽救 PPT1 诱导的小鼠卵母细胞损伤,不仅通过调节氧化应激,还通过与 PPT1 结合以调节其溶酶体降解。总之,我们的数据表明 PPT1 通过调节微管蛋白棕榈酰化参与卵母细胞衰老,提供了氧化应激调节蛋白质棕榈酰化的证据,并揭示了卵母细胞衰老的新机制。