title: G0/G1 phase arrest and apoptosis induced by manganese chloride on cultured rat astrocytes and protective effects of riluzole.
abstract: Occupational or environmental exposure to excessive Mn would cause manganism, which is resembled Parkinson disease. However, the mechanism underlying manganism is still unknown. It had been documented that astrocytes play important roles in physiological function in brain. Therefore, in the present study, the cultured astrocytes were exposed to 0, 125, 250, and 500 μM MnCl(2), and cell viability, lactate dehydrogenase (LDH) leakage, morphological change, cell cycle progression, and apoptosis were determined. In addition, 100 μM riluzole (a glutamatergic modulator) was pretreated for 6 h before no MnCl(2) exposure or 500 μM MnCl(2) exposure. The results showed that cell viability inhibited, LDH leakage elevated, morphology injured, G(0)/G(1) phase cell cycle arrested, and apoptosis rate increased in a concentration-dependent manner. Further investigation indicated that riluzole pretreatment reversed cytotoxicity, cell cycle aberration, and apoptosis on astrocytes caused by MnCl(2). These results suggested that MnCl(2) could cause cytotoxicity, cell cycle arrest, and apoptosis concentration-dependently; riluzole might antagonize Mn toxicity on astrocytes.
authors.affiliation: 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
authors.forename: Donghui
authors.initials: D
authors.lastname: Xu
authors.forename: Bin
authors.initials: B
authors.lastname: Xu
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Xu
authors.forename: Yawen
authors.initials: Y
authors.lastname: Tian
authors.forename: Wanyu
authors.initials: W
authors.lastname: Feng
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Haibo
authors.initials: H
authors.lastname: Yang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002712:Chlorides / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D017895:Manganese Compounds / Q000037:antagonists & inhibitors*; D020149:Manganese Poisoning / Q000473:pathology* / Q000517:prevention & control*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016192:Resting Phase, Cell Cycle / Q000187:drug effects*; D019782:Riluzole / Q000494:pharmacology*; D013778:Tetrazolium Salts; D013844:Thiazoles
chemical_list: D002712:Chlorides; D004396:Coloring Agents; D017895:Manganese Compounds; D018696:Neuroprotective Agents; D013778:Tetrazolium Salts; D013844:Thiazoles; D019782:Riluzole; D007770:L-Lactate Dehydrogenase; C022616:thiazolyl blue; C025340:manganese chloride