Department of Reproductive Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.
Celloxess LLC, 830 Bear Tavern Road, Ewing, NJ 08628, USA.
Oxid Med Cell Longev. 2020 Jul 29;2020:5909306. doi: 10.1155/2020/5909306. eCollection 2020.
Using a surgically induced varicocele rat model, we show here strong evidence that the misfolded/unfolded protein response that is part of the stress response of the endoplasmic reticulum (ER) is activated in the varicocele testis (VCL), leading to the induction of apoptosis. To support this hypothesis, it is observed that the spliced variant of the X-box protein 1 (XBP1s), resulting from the activation of the inositol-requiring enzyme 1 (IRE1) membrane sensor, is significantly more represented in VCL testicular extracts. The activation of the IRE1/XBP1s pathway is also supported by the observation that the VCL testes show an increase phosphorylation of the c-Jun-kinase (JNK) known to be one intermediate of this pathway and an increased level of caspase-3, the terminal apoptotic effector, partly explaining the apoptotic status of the VCL testis.
在这里，我们使用一种手术诱导的精索静脉曲张大鼠模型，有力地证明了内质网（ER）应激反应的错误折叠/未折叠蛋白反应在精索静脉曲张睾丸（VCL）中被激活，导致细胞凋亡。为了支持这一假说，我们观察到 X 盒结合蛋白 1（XBP1s）的剪接变体，它是肌醇需求酶 1（IRE1）膜传感器激活的结果，在 VCL 睾丸提取物中显著增加。IRE1/XBP1s 途径的激活还得到了观察的支持，即 VCL 睾丸显示出 c-Jun-激酶（JNK）的磷酸化水平增加，众所周知，JNK 是该途径的一个中间产物，同时 caspase-3 的水平也增加，caspase-3 是凋亡的终末效应物，部分解释了 VCL 睾丸的凋亡状态。
