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High-mobility group box 1 regulates cytoprotective autophagy in a mouse spermatocyte cell line (GC-2spd) exposed to
1Key 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.
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.
Insights
High-mobility group box 1 protein (HMGB1) enhances autophagy, a cellular defense mechanism, against cadmium-induced toxicity in mouse germ cells, improving cell survival.
Area of Science:
- Toxicology
- Cell Biology
- Reproductive Science
Background:
- Cadmium (Cd) is a toxic pollutant linked to male infertility and testicular germ cell apoptosis.
- The role of autophagy in germ cells following Cd exposure remains unclear.
Purpose of the Study:
- To investigate the role of high-mobility group box 1 protein (HMGB1) in cadmium-induced autophagy in mouse spermatocyte cells.
- To understand the protective function of autophagy against Cd toxicity.
Main Methods:
- Utilized a mouse spermatocyte cell line (GC-2spd) exposed to Cadmium (Cd).
- Investigated the effects of Cd on autophagy markers and cell viability.
- Examined the involvement of high-mobility group box 1 protein (HMGB1) and rapamycin (RAP) treatment.
Main Results:
- Cadmium exposure significantly elevated autophagy (increased LC3-II levels) in GC-2spd cells.
- Autophagy appeared to reduce cadmium-induced cytotoxicity and cell death.
- HMGB1 levels increased with Cd exposure, correlating with elevated autophagy.
Conclusions:
- HMGB1-induced autophagy acts as a defense mechanism against cadmium cytotoxicity in germ cells.
- This autophagy pathway may play a crucial role in protecting male reproductive health from environmental toxins.