Ou Z, Chen Y, Niu X, He W, Song B, Fan D, Sun X
Key Laboratory for Major Obstetric Diseases of Guangdong Province, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, People's Republic of China.
Ir J Med Sci. 2017 Nov;186(4):1041-1050. doi: 10.1007/s11845-017-1595-y. Epub 2017 Apr 7.
Cadmium (Cd) is an environmental and industrial pollutant that induces a broad spectrum of toxicological effects, influences a variety of human organs, and is associated with poor semen quality and male infertility. Increasing evidence demonstrates that Cd induces testicular germ cell apoptosis in rodent animals. However, the specific effect of Cd exposure on autophagy in germ cells is poorly understood.
We investigate the role of high-mobility group box 1 protein (HMGB1), a ubiquitous nuclear protein, on Cd-evoked autophagy in a mouse spermatocyte cell line (GC-2spd).
Our data have shown that autophagy was significantly elevated in GC-2spd cells exposed to Cd. Furthermore, there was a reduction in rapamycin (RAP)-mediated apoptosis. In addition, Cd exposure reduced cell viability, which is an effect that could be significantly inhibited by RAP treatment. These results indicate that autophagy appears to serve a positive function in reducing Cd-induced cytotoxicity. In addition, HMGB1 increased coincident with the processing of LC3-I to LC3-II. Thus, the upregulation of HMGB1 increases LC3-II levels.
Our data suggest that HMGB1-induced autophagy appears to act as a defense/survival mechanism against Cd cytotoxicity in GC-2spd cells.
镉（Cd）是一种环境和工业污染物，可引发广泛的毒理学效应，影响人体多个器官，并与精液质量差和男性不育有关。越来越多的证据表明，镉可诱导啮齿动物睾丸生殖细胞凋亡。然而，镉暴露对生殖细胞自噬的具体影响尚不清楚。
我们研究了一种普遍存在的核蛋白——高迁移率族蛋白B1（HMGB1）在小鼠精母细胞系（GC-2spd）中镉诱发的自噬中的作用。
我们的数据表明，暴露于镉的GC-2spd细胞中自噬显著增强。此外，雷帕霉素（RAP）介导的细胞凋亡减少。此外，镉暴露降低了细胞活力，而RAP处理可显著抑制这种作用。这些结果表明，自噬似乎在降低镉诱导的细胞毒性方面发挥着积极作用。此外，HMGB1的增加与LC3-I向LC3-II的转化同时发生。因此，HMGB1的上调增加了LC3-II水平。
我们的数据表明，HMGB1诱导的自噬似乎是GC-2spd细胞中对抗镉细胞毒性的一种防御/存活机制。
