title: Protective effects of Alpha-lipoic acid on MeHg-induced oxidative damage and intracellular Ca(2+) dyshomeostasis in primary cultured neurons.
abstract: Methylmercury (MeHg) is one of the ubiquitous environmental toxicant that leads to long-lasting neurological deficits in animals and humans. However, the mechanisms of MeHg-induced neuronal cell death are incompletely understood. Treatment of neuronal cells with MeHg (0-2 μM) for 0.5-12 h, or pretreated with LA (12.5-100 μM) for 0.5-6 h resulted in toxic effects of primary cultured neurons concentration- and time-dependently. For further experiments, 12.5, 25, and 50 μM of LA pretreatment for 3 h followed by 1 μM MeHg for 6 h were performed for the examination of the responses of neurons. Exposure of MeHg resulted in damages of neurons, which were shown by a loss of cell viability, and supported by high levels of lactate dehydrogenase (LDH) release, apoptosis, and morphological changes. In addition, neurons were sensitive to MeHg-mediated oxidative stress, a finding that is consistent with ROS over-production, leading to decrease Ca(2+)-ATPase activity and increase intracellular free calcium. Moreover, expressions of NMDA receptor subunits in neurons were down-regulated after MeHg exposure, and expression of NR2A mRNA and protein were much more sensitive to MeHg than those of NR1 and NR2B. On the contrary, pretreatment with LA presented a concentration-dependent prevention against MeHg-mediated cytotoxic effects of neurons. In conclusion, present results showed that oxidative stress and intracellular Ca(2+ )dyshomeostasis resulting from MeHg exposure contributed to neuronal injury. LA could attenuate MeHg-induced neuronal toxicity via its antioxidant properties in primary cultured neurons.
authors.affiliation: a Department of Environmental Health, School of Public Health , China Medical University , Shenyang , People's Republic of China.
authors.forename: Tianyao
authors.initials: T
authors.lastname: Yang
authors.affiliation: a Department of Environmental Health, School of Public Health , China Medical University , Shenyang , People's Republic of China.
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Xu
authors.affiliation: a Department of Environmental Health, School of Public Health , China Medical University , Shenyang , People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: a Department of Environmental Health, School of Public Health , China Medical University , Shenyang , People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.affiliation: a Department of Environmental Health, School of Public Health , China Medical University , Shenyang , People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Deng
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D017209:Apoptosis / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D008063:Thioctic Acid / Q000008:administration & dosage*
chemical_list: D000975:Antioxidants; D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D008063:Thioctic Acid
keywords: Alpha-lipoic acid; Ca2+ dyshomeostasis; methylmercury; oxidative stress; reactive oxygen species