title: Oxidative stress involves in astrocytic alterations induced by manganese.
abstract: It is hypothesized that manganese neurotoxicity could be secondary to a diminution of cellular protective and scavenger mechanisms. Since manganese is known to be sequestered in glial cells, we investigated possible neurotoxic mechanisms involving astrocytes in vitro. Astrocytes differentiated into process-bearing stellate cells in response to manganese treatment. Manganese concentration dependently decreased cellular DNA synthesis, glial fibrillary acidic protein expression, energy production, antioxidant capacity, and glutamate transporter activity. In contrast, manganese increased glutamine synthetase protein expression and cytokine-stimulated interleukin 6 mRNA expression. Under the concentration of 0.1 mM, manganese chloride caused no significant astrocyte death even up to 48 h after treatment. That is, these astrocytic alterations proceeded before the onset of cell demise. As a possible mediator of manganese-derived alterations, we determined intracellular redox state in astrocytes. Manganese time-dependently changed intracellular redox potential into oxidized state. The influx of manganese and its resultant oxidative stress was essential to most of the alterations, except for the action on stellation. Astrocytes are central component of the brain's antioxidant defense. Therefore, the observations suggest that dysfunction of astrocytes possibly involved in neurotoxic action of manganese.
authors: Department of Education and Research, Taichung Veterans General Hospital, No. 160, Sec. 3, Taichung-Gang Road, Taichung, 40705, Republic of China. cjchen@vghtc.vghtc.gov.tw
authors: Chun-Jung
authors: CJ
authors: Chen
authors: Su-Lan
authors: SL
authors: Liao
mesh_terms: D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt / Q000494:pharmacology; D027322:Amino Acid Transport System X-AG / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D016207:Cytokines / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008345:Manganese / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D027322:Amino Acid Transport System X-AG; D000975:Antioxidants; D002614:Chelating Agents; D016207:Cytokines; D005904:Glial Fibrillary Acidic Protein; D015850:Interleukin-6; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D008345:Manganese; D014013:1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium Salt; D004247:DNA; D005974:Glutamate-Ammonia Ligase