Abstract
Methylmercury (MeHg), an organic form of deleterious metalloid mercury, usually exists in the environmental and industrial pollutant, which has been reported to cause serious damage in mammalian, including central nervous and respiratory system. Comparatively, the effects of MeHg-induced cell death in sertoli cells are the most unclear. Here, we investigated the toxicological effects and possible mechanisms of MeHg in mouse sertoli cells (TM4 cells). Treatment of TM4 cells with MeHg (0.25-5μM) significantly reduced cell viability and caused oxidative stress damages (such as reactive oxygen species (ROS) formation, lipid peroxidation (LPO) production and intracellular glutathione depletion). MeHg also induced the increased population of sub-G1 hypodiploid and annexin V binding cells, dysfunction of mitochondria, activation of poly (ADP-ribose) polymerase, caspase cascades, and mitogen-activated protein kinases (MAPKs), which features the MAPK-mediated mitochondria-dependent apoptosis. Furthermore, MeHg-exposd TM4 cells could trigger endoplasmic reticulum (ER) stress-regulated death signals such as ER stress-related markers (GRP 78, GRP 94, CHOP, XBP-1) expressions, procaspase-12 cleavage and calpain activities. These MeHg-induced apoptosis-related signals could be effectively reversed by pretreatment with N-acetylcysteine (NAC). To sum up, these results indicated that MeHg-induced oxidative stress causes sertoli cells apoptosis involved in MAKPs-mediated mitochondria-dependent and ER stress signals pathway.
Keyword: Methylmercury (MeHg); Sertoli cells; Apoptosis; Oxidative stress; Mitochondrial dysfunction; ER stress.
