Integrated stress response mediates HSP70 to inhibit testosterone synthesis in aging testicular Leydig cells

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
Junqiang Zhang , Hui Yu , Yongqi Fan , Longmei Wu , Yuan Fang , Zhaolian Wei , Zhiguo Zhang , Yunxia Cao
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Abstract

The integrated stress response (ISR) is implicated in age-related diseases, while the molecular chaperone heat shock protein 70 (HSP70) can facilitate proper protein folding. However, the regulatory mechanism of ISR in insufficient testosterone synthesis of aging Leydig cells (LCs) remains unclear. This study aims to elucidate the regulatory role of ISR in inadequate testosterone synthesis of aging LCs. We observed a positive correlation between testosterone and HSP70 levels, which were found to be decreased in elderly men. ISR was detected in testicular tissue from old mice. The expression of testosterone synthesis related protein and the content of testosterone decreased in testicular tissue of old mice. Conversely, inhibition of the integrated stress response in testicular tissue led to an increase in steroid synthase expression among old mice. Furthermore, inhibiting ISR specifically within aging LCs resulted in enhanced protein translation efficiency and increased expression levels of new HSP70 and steroidogenic acute regulatory protein (StAR). These findings suggest that ISR occurrence within aging LCs affects StAR protein expression through regulation of HSP70-mediated translation, consequently impairing testosterone synthesis.
综合应激反应介导 HSP70 抑制老化睾丸雷蒂格细胞中睾酮的合成。
综合应激反应(ISR)与年龄相关疾病有关,而分子伴侣热休克蛋白 70(HSP70)可促进蛋白质的正常折叠。然而,综合应激反应在老化的雷迪格细胞(LCs)睾酮合成不足中的调控机制仍不清楚。本研究旨在阐明ISR在老化LCs睾酮合成不足中的调控作用。我们观察到睾酮与 HSP70 水平之间存在正相关,而老年男性的 HSP70 水平有所下降。在老年小鼠的睾丸组织中检测到了 ISR。在老年小鼠的睾丸组织中,睾酮合成相关蛋白的表达和睾酮的含量都有所下降。相反,抑制睾丸组织中的综合应激反应会导致老年小鼠体内类固醇合成酶的表达增加。此外,特异性抑制衰老 LCs 中的 ISR 可提高蛋白质翻译效率,增加新 HSP70 和类固醇生成急性调节蛋白(StAR)的表达水平。这些研究结果表明,衰老 LCs 中 ISR 的发生会通过调节 HSP70 介导的翻译影响 StAR 蛋白的表达,从而损害睾酮的合成。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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