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首页> 外文期刊>Cell and Tissue Research >Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR processing
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Testicular STAC3 regulates Leydig cell steroidogenesis through potentiating mitochondrial membrane potential and StAR processing

机译:睾丸STAC3通过增强线粒体膜潜力和星加工来调节Leydig细胞系序列化

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摘要

SH3 and cysteine-rich protein 3 (STAC3), a small adapter protein originally identified as a core component of excitation-contraction coupling machinery, regulates the voltage-induced Ca2+ release in skeletal muscle. However, the possibility of additional, as yet unknown, non-muscle effects of STAC3 cannot be ruled out. Herein, we provide the evidence for the expression and functional involvement of STAC3 in spermatogenesis. STAC3 expression was localized in the testicular interstitium of rodent and human testes. By using the cytotoxic drug ethylene dimethane sulfonate (EDS), STAC3 expression was observed to be decreased sharply in rat testis after selective withdrawal of Leydig cells (LCs), and reappeared immediately after LCs repopulation, indicating that testicular expression of STAC3 mainly stems from LCs. From a functional standpoint, in vivo lentiviral vector-mediated suppression of STAC3 resulted in a significant decrease in testosterone production, and thereafter caused impairment of male fertility by inducing oligozoospermia and asthenospermia. The indispensible involvement of STAC3 in testicular steroidogenesis was validated using the in vivo knockdown model with isolated primary LCs as well as in vitro experiments with primary LCs. By generating the TM3(Stac3-/-) cells, we further revealed that STAC3 depletion attenuated mitochondrial membrane potential and StAR processing in db-cAMP-stimulated LCs. Thus, the inhibitory effect of STAC3 deficiency on testicular steroidogenesis may be ascribed to a disturbed mitochondrial homeostasis. Collectively, the present results strongly suggest that STAC3 may function as a novel regulator linking mitochondrial homeostasis and testicular steroidogenesis in LCs. Our data underscore an unexpected reproductive facet of this muscle-derived factor.
机译:SH3和富含半胱氨酸的蛋白3(STAC3)是一种小的衔接蛋白,最初被确定为兴奋-收缩耦合机制的核心成分,调节骨骼肌中电压诱导的Ca2+释放。然而,不能排除STAC3可能会产生额外的、尚不清楚的非肌肉效应。在此,我们为STAC3在精子发生中的表达和功能参与提供了证据。STAC3表达定位于啮齿动物和人类睾丸间质。通过使用细胞毒性药物二甲基磺酸乙烯酯(EDS),在大鼠睾丸中观察到STAC3的表达在选择性退出睾丸间质细胞(LCs)后急剧下降,并在LCs重新填充后立即重新出现,表明STAC3的睾丸表达主要来源于LCs。从功能角度来看,体内慢病毒载体介导的STAC3抑制导致睾酮生成显著减少,随后通过诱导少精子症和弱精子症导致男性生育能力受损。STAC3在睾丸类固醇生成中的不可或缺的作用,通过分离原发性LCs的体内击倒模型以及原发性LCs的体外实验进行了验证。通过产生TM3(Stac3-/-)细胞,我们进一步揭示了Stac3缺失减弱了db-cAMP刺激的LCs中的线粒体膜电位和星形加工。因此,STAC3缺乏对睾丸类固醇生成的抑制作用可能归因于线粒体内稳态的紊乱。总的来说,目前的结果强烈表明STAC3可能是LCs中连接线粒体内稳态和睾丸类固醇生成的新型调节器。我们的数据强调了这种肌肉衍生因子的一个意想不到的生殖方面。

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