In vitro effect of manganese chloride exposure on reactive oxygen species generation and respiratory chain complexes activities of mitochondria isolated from rat brain.
Manganese (Mn) is known to induce mitochondrial dysfunction in excessive dose; however the mechanisms underlying its action are not elucidated clearly. To determine if Mn2+ can act directly on mitochondria or indirectly by producing reactive oxygen species (ROS), isolated mitochondria were exposed to different concentration of Mn2+ (5, 50, 500, 1000 microM). ROS generation, respiratory control ratio (RCR), mitochondrial membrane potential (MMP) and respiratory chain complexes activities were investigated. Dose-dependent inhibition of respiratory chain complexes and induction of ROS were observed; these changes were paralleled by decreasing of respiratory control ratio (RCR) both with succinate or glutamate + malate. Further investigation indicated that the membrane potential determined by Rhodamine123 release decreased after MnCl2 exposure at 1000 microM. In addition, effects of the antioxidants NAC (500 microM), GSH (500 microM) and Vitamin C (500 microM) were studied at 500 microM Mn2+. The results indicate that the effect of Mn2+ exposure on respiratory chain is not site-specific, and antioxidants can protect the mitochondria function by reducing the formation of free radicals.
Zhang
Surong
S
Department of Toxicology, School of Public Health, Peking University Health Science Center, Beijing 100083, PR China.
Fu
Juanling
J
Zhou
Zongcan
Z
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D001921:Brain / Q000648:ultrastructure*; D002712:Chlorides / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D045304:Cytochromes c / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004579:Electron Transport / Q000187:drug effects* / Q000502:physiology; D005978:Glutathione / Q000494:pharmacology; D017895:Manganese Compounds / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D009247:NADH, NADPH Oxidoreductases / Q000187:drug effects / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020112:Rhodamine 123; D013385:Succinate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000187:drug effects
D002712:Chlorides; D004338:Drug Combinations; D017895:Manganese Compounds; D017382:Reactive Oxygen Species; D014451:Ubiquinone; D020112:Rhodamine 123; D045304:Cytochromes c; D013385:Succinate Dehydrogenase; D009247:NADH, NADPH Oxidoreductases; D005978:Glutathione; D001205:Ascorbic Acid; C025340:manganese chloride; D000111:Acetylcysteine