Proteasome inhibition is associated with manganese-induced oxidative injury in PC12 cells.
Manganese has been known to induce neurological disorders similar to Parkinson's disease. The dysfunction of ubiquitin-proteasome system, a pathway involved in detoxification and targeting of damaged proteins, is connected with Parkinson's disease pathogenesis. Oxidative stress may be involved in Parkinson's disease, and may also be associated with manganese-induced neurotoxicity. In the present study, we determined the effects of manganese chloride on proteasome activity in PC12 cells. Furthermore, we investigated the relationship between oxidative stress and the change of proteasome activity. The proteasome activity of PC12 cells was measured by an ELISA method. Selective oxidative stress parameters, including malondialdehyde and protein carbonyl, were measured in PC12 cells treated with manganese chloride. Cell survival and apoptosis were measured by methyl thiazolyl tetrazolium and terminal transferase-mediated dUTP nick end-labeling. In our research, manganese chloride exposure inhibited the activity of proteasome and induced oxidative stress. Both can be reversed by antioxidant agent N-acetylcysteine. N-acetylcysteine also inhibited the cytotoxicity induced by manganese chloride. In conclusion, our results imply that proteasome inhibition may be associated with manganese-induced cytotoxicity in dopaminergic neurons, which may be connected with oxidative damage.
Cai
Tongjian
T
Department of Occupational and Environmental Health, Fourth Military Medical University, Xi'an 710032, China.
Yao
Ting
T
Li
Yan
Y
Chen
Yaoming
Y
Du
Kejun
K
Chen
Jingyuan
J
Luo
Wenjing
W
D000111:Acetylcysteine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count / Q000379:methods; D002712:Chlorides / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D020287:In Situ Nick-End Labeling; D017895:Manganese Compounds / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D016716:PC12 Cells / Q000187:drug effects / Q000473:pathology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D013778:Tetrazolium Salts; D013844:Thiazoles; D014131:Trace Elements / Q000009:adverse effects*
D000975:Antioxidants; D002712:Chlorides; D017895:Manganese Compounds; D013778:Tetrazolium Salts; D013844:Thiazoles; D014131:Trace Elements; D046988:Proteasome Endopeptidase Complex; C022616:thiazolyl blue; C025340:manganese chloride; D000111:Acetylcysteine