Z Ou1, Y Chen1, X Niu1, W He1, B Song1, D Fan1, X Sun2. 1. 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. 2. 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. xiaofangsun@gzhmu.edu.cn.
Abstract
BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Our data suggest that HMGB1-induced autophagy appears to act as a defense/survival mechanism against Cd cytotoxicity in GC-2spd cells.
BACKGROUND: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. METHODS: 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). RESULTS: 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. CONCLUSIONS: Our data suggest that HMGB1-induced autophagy appears to act as a defense/survival mechanism against Cdcytotoxicity in GC-2spd cells.
Authors: Julian J Lum; Daniel E Bauer; Mei Kong; Marian H Harris; Chi Li; Tullia Lindsten; Craig B Thompson Journal: Cell Date: 2005-01-28 Impact factor: 41.582
Authors: Peter Huebener; Geum-Youn Gwak; Jean-Philippe Pradere; Catarina M Quinzii; Richard Friedman; Chyuan-Sheng Lin; Chad M Trent; Ingmar Mederacke; Enpeng Zhao; Dianne H Dapito; Yuxi Lin; Ira J Goldberg; Mark J Czaja; Robert F Schwabe Journal: Cell Metab Date: 2014-03-04 Impact factor: 27.287