赛珀美林通过内质网膜-线粒体合,诱导塞尔托利细胞的亡,其中涉及IP3R1-GRP75-VDAC1
Rui Zhang1, Xu-Xu Wang1, Jia-Fei Xie1
1Key Lab of Environment and Health, School of Public Health, Xuzhou Medical University, 209 Tong-Shan Road, Xuzhou 221004, Jiangsu, China; Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, Jiangsu 221004, China.
Reproductive toxicology (Elmsford, N.Y.)
|January 31, 2024
概括
甲 (CYP) 是一种内分泌干扰物,可在小鼠塞尔托利细胞中引发亡. 这通过内分泌网膜-线粒体合发生,特别是涉及IP3R1-GRP75-VDAC1,导致过载和细胞死亡.
科学领域:
- 内分泌学 在内分泌学.
- 毒理学 毒理学 毒理学
- 细胞生物学 细胞生物学
背景情况:
- 甲 (Cypermethrin,简称CYP) 是一种广泛使用的甲类杀虫剂和内分泌干扰化学物质 (EDC).
- CYP表现出抗雄激素活性,有助于男性生殖毒理学,但其精确的机制尚不清楚.
- 塞尔托利细胞对男性生殖功能至关重要,它们的细胞亡会损害生育能力.
研究的目的:
- 为了研究CYP对小鼠TM4塞尔托利细胞的亡的影响.
- 阐明细胞内膜网膜 (ER) -线粒体合,特别是IP3R1-GRP75-VDAC1通路在CYP诱导的亡中的作用.
主要方法:
- TM4细胞被培养并用不同度的CYP处理.
- 使用流式细胞计量评估了亡.
- 使用光探针测量线粒体 (Ca2+) 水平.
- 分析了ER-线粒体的合和蛋白质的表达,通过传输电子显微镜,共聚焦显微镜,和西部涂抹.
主要成果:
- CYP显著增加了TM4细胞的亡率.
- CYP提高了亡标记物的表达,包括裂开的caspase-3和裂开的PARP.
- 线粒体Ca2+度和ER-线粒体合被CYP治疗显著增强.
- 在暴露于CYP后,IP3R1,GRP75和VDAC1蛋白的表达显著上调.
结论:
- 在TM4 Sertoli细胞中,CYP诱导了亡.
- 这一过程由增强的ER-线粒体合介导,涉及IP3R1-GRP75-VDAC1复合体.
- 由CYP诱导的线粒体过载是驱动塞尔托利细胞亡的关键机制.
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