1. The effects of mTOR or Vps34-mediated autophagy on methylmercury-induced neuronal apoptosis in rat cerebral cortex.
- Author
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Ni L, Wei Y, Pan J, Li X, Xu B, Deng Y, Yang T, and Liu W
- Subjects
- Adenine analogs & derivatives, Adenine pharmacology, Animals, Cerebral Cortex pathology, Class III Phosphatidylinositol 3-Kinases antagonists & inhibitors, Dose-Response Relationship, Drug, Female, Male, Neurons drug effects, Rats, Wistar, Sirolimus pharmacology, TOR Serine-Threonine Kinases antagonists & inhibitors, Rats, Apoptosis drug effects, Autophagy physiology, Cerebral Cortex drug effects, Class III Phosphatidylinositol 3-Kinases metabolism, Methylmercury Compounds toxicity, TOR Serine-Threonine Kinases metabolism
- Abstract
Methylmercury (MeHg) is a environmental contaminant, which can induce neurotoxic effects. So far, the exact molecular mechanisms of autophagy and its effect on apoptosis in MeHg-induced neurotoxicity have not been elucidated. Here, rats were exposed to MeHg (4, 8, or 12 μmol/kg) for 4 weeks to evaluate the dose-effect relationship between MeHg and apoptosis, or autophagy in cerebral cortex. On this basis, rapamycin (Rapa) or 3-methyladenine (3-MA) was administrated to further explore the regulatory mechanisms of autophagy on MeHg-induced neuronal apoptosis. The pathological changes, autophagy or apoptosis levels, expression of autophagic or apoptotic-associated factors such as mTOR, S6K1, 4EBP1, Vps34, Beclin1, p62, LC3, Bcl-2/Bax, caspase, or MAPKs were investigated. Results showed that MeHg dose-dependently induced pathological changes in cerebral cortex, and the levels of autophagy and apoptosis were increased. Furthermore, Rapa pretreatment antagonized MeHg-induced apoptosis, whereas 3-MA further aggravated apoptosis, which were supported by findings that Rapa activated mTOR-mediated autophagy while 3-MA inhibited Vps34-related autophagy, further affect neuronal apoptosis through regulation of apoptotic factors mentioned above. In conclusion, the findings indicated that MeHg dose-dependently induced autophagy or apoptosis, and mTOR or Vps34 may play important roles in mediating autophagy, which further regulated apoptosis through MAPKs or mitochondrial apoptosis pathways., (Copyright © 2021 Elsevier Ltd. All rights reserved.)
- Published
- 2021
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