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Published on: February 9, 2014
Microcystin-LR induces autophagy and apoptosis in rat Sertoli cells in vitro
Yu Chen1, Yuan Zhou, Xueting Wang
1Immunology and Reproduction Biology Laboratory, Medical School, Nanjing University, Nanjing, Jiangsu 210093, China; Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093, China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu 210093, China.
Abstract:
Although microcystin-LR (MC-LR) produced by cyanobacteria has been demonstrated with strong reproductive toxicity, the mechanisms remain unclear. This study aimed to probe the effects of MC-LR on induction of autophagy in Sertoli cells, as well as the relationship between autophagy and apoptosis. After exposure to various concentrations of MC-LR for 24 or 48 h, cell viability and membrane integrity were significantly decreased under high MC-LR conditions (50-500 nM). The autophagosome marker protein LC3 was increased at mild MC-LR concentrations (0.5-5 nM). However, autophagosomes accumulated to their peak level under high MC-LR conditions in parallel with significantly up-regulated apoptosis. Treatment with an autophagy inhibitor (3-MA) abrogated autophagosome accumulation and apoptosis. This study demonstrated that MC-LR had toxic effects on Sertoli cells by inducing autophagy and apoptosis. The autophagosome accumulation may be involved in the apoptosis induced by MC-LR.
Insights
Microcystin-LR (MC-LR) from cyanobacteria harms reproductive cells. This study shows MC-LR induces autophagy and apoptosis in Sertoli cells, linking these processes to its toxicity.
Area of Science:
- Environmental Toxicology
- Cell Biology
- Reproductive Toxicology
Background:
- Cyanobacteria produce microcystin-LR (MC-LR), a toxin with known reproductive toxicity.
- The precise mechanisms underlying MC-LR's toxicity, particularly in Sertoli cells, remain incompletely understood.
Purpose of the Study:
- To investigate the impact of MC-LR on autophagy induction in Sertoli cells.
- To elucidate the relationship between MC-LR-induced autophagy and apoptosis in these cells.
Main Methods:
- Sertoli cells were exposed to varying concentrations of MC-LR (0.5-500 nM) for 24 or 48 hours.
- Cell viability, membrane integrity, and the autophagosome marker LC3 were assessed.
- The role of autophagy in MC-LR toxicity was examined using an autophagy inhibitor (3-MA).
Main Results:
- MC-LR exposure at high concentrations (50-500 nM) reduced Sertoli cell viability and membrane integrity.
- Mild MC-LR concentrations (0.5-5 nM) increased the autophagosome marker LC3.
- High MC-LR concentrations led to significant autophagosome accumulation and increased apoptosis, which was mitigated by 3-MA.
Conclusions:
- MC-LR exerts toxic effects on Sertoli cells through the induction of both autophagy and apoptosis.
- Autophagosome accumulation appears to be a key factor in the apoptosis pathway triggered by MC-LR exposure.
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