Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress.
Protein palmitoylation-mediated palmitic acid sensing causes blood-testis barrier damage via inducing ER stress.
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蛋白质棕榈酰化介导的棕榈酸传感通过诱导内质网应激导致血睾屏障损伤
DOI：
10.1016/j.redox.2022.102380
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发表时间：
2022-08
期刊：
影响因子：
11.4
通讯作者：
Yao, Bing
中科院分区：
文献类型：
--
作者：
Ge, Xie;He, Zhaowanyue;Cao, Chun;Xue, Tongmin;Jing, Jun;Ma, Rujun;Zhao, Wei;Liu, Ling;Jueraitetibaike, Kadiliya;Ma, Jinzhao;Feng, Yuming;Qian, Zhang;Zou, Zhichuan;Chen, Li;Fu, Chuanhai;Song, Ninghong;Yao, Bing
关键词：
血睾丸屏障（BTB）损伤促进精子发生功能障碍，这是男性不育的一个重要原因。血脂异常与男性不育有关，但主要的危险脂质及其潜在机制尚不清楚。在本研究中，我们首次发现palmitic acid （PA）在严重精子异常症患者中升高，抑制素B （inhibin B）降低，这促使我们探索PA对Sertoli细胞的影响。我们观察到PA对BTB的损伤。显微成像和动态观察显示了PA对内质网（ER）的渗透及其对ER结构的破坏，并证实了随之而来的内质网应激介导PA诱导的Sertoli细胞屏障破坏。值得注意的是，我们证明了异常蛋白棕榈酰化在pa诱导的支持细胞屏障功能障碍中的关键作用。一种内质网蛋白Calnexin被筛选出来，并被证明参与了这一过程，抑制其棕榈酰化显示出改善作用。我们还发现ω-3多不饱和脂肪酸下调Calnexin棕榈酰化，减轻BTB功能障碍。我们的研究结果表明，PA诱导的棕榈酰化失调在BTB破坏和随后的精子发生功能障碍中起着关键作用，这表明棕榈酰化蛋白可能是男性不育的治疗靶点。在严重精子异常患者中发现循环PA升高。pa诱导的支持细胞过度棕榈酰化导致内质网应激和BTB损伤。内质网蛋白钙连蛋白的棕榈酰化调节支持细胞的屏障功能。ω-3 PUFAs可改善pa诱导的支持细胞损伤和过度棕榈酰化。
Blood-testis barrier (BTB) damage promotes spermatogenesis dysfunction, which is a critical cause of male infertility. Dyslipidemia has been correlated with male infertility, but the major hazardous lipid and the underlying mechanism remains unclear. In this study, we firstly discovered an elevation of palmitic acid (PA) and a decrease of inhibin B in patients with severe dyszoospermia, which leaded us to explore the effects of PA on Sertoli cells. We observed a damage of BTB by PA. PA penetration to endoplasmic reticulum (ER) and its damage to ER structures were exhibited by microimaging and dynamic observation, and consequent ER stress was proved to mediate PA-induced Sertoli cell barrier disruption. Remarkably, we demonstrated a critical role of aberrant protein palmitoylation in PA-induced Sertoli cell barrier dysfunction. An ER protein, Calnexin, was screened out and was demonstrated to participate in this process, and suppression of its palmitoylation showed an ameliorating effect. We also found that ω-3 poly-unsaturated fatty acids down-regulated Calnexin palmitoylation, and alleviated BTB dysfunction. Our results indicate that dysregulated palmitoylation induced by PA plays a pivotal role in BTB disruption and subsequent spermatogenesis dysfunction, suggesting that protein palmitoylation might be therapeutically targetable in male infertility. An elevation of circulating PA was identified in patients with severe dyszoospermia. PA-induced over-palmitoylation in Sertoli cells leads to ER stress and BTB damage. The palmitoylation of the ER protein Calnexin regulates Sertoli cell barrier function. ω-3 PUFAs ameliorate PA-induced damage and over-palmitoylation in Sertoli cells.
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影响因子：
5.9
作者：
Bermúdez-Cardona J;Velásquez-Rodríguez C
通讯作者：
Velásquez-Rodríguez C
影响因子：
3.7
作者：
Fullston T;Ohlsson-Teague EM;Print CG;Sandeman LY;Lane M
通讯作者：
Lane M
DOI：
10.1186/s12958-018-0401-7
发表时间：
2018-09-22
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Hu X;Ding Z;Hong Z;Zou Z;Feng Y;Zhu R;Ma J;Ge X;Li C;Yao B
通讯作者：
Yao B
影响因子：
2.4
作者：
Hu, Xuechun;Ge, Xie;Yao, Bing
通讯作者：
Yao, Bing
影响因子：
4.8
作者：
Jiang, Min;Hu, Junping;Tseng, Gea-Ny
通讯作者：
Tseng, Gea-Ny