Mitochondrial cytochrome c oxidase subunit III is selectively down-regulated by aluminum exposure in PC12S cells.
Aluminum (Al) has been implicated in several neurological diseases including dialysis dementia and Alzheimer's disease (AD). One possible mechanism of Al neurotoxicity could involve alteration of mitochondrial gene expression. We exposed PC12 cells to 0.1-100 microM AlCl3 for 6h at pH 7.4. Internalized Al, measured by atomic absorption spectrometry, was linearly proportional to the extracellular Al concentration. Northern blot analyses showed that cytochrome c oxidase subunit III (COX III) mRNA was significantly reduced by 70% after addition of 1 microM AlCl3. Higher concentrations of AlCl3 did not show a significant further effect. These results suggest that Al neurotoxicity involves a specific impairment of cytochrome c oxidase.
Bosetti
F
F
Section on Brain Physiology and Metabolism, National Institute on Aging, NIH, Bethesda, MD 20892, USA.
Solaini
G
G
Tendi
E A
EA
Chikhale
E G
EG
Chandrasekaran
K
K
Rapoport
S I
SI
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000493:pharmacokinetics / Q000633:toxicity*; D000544:Alzheimer Disease / Q000378:metabolism; D000818:Animals; D001252:Astringents / Q000493:pharmacokinetics / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002712:Chlorides / Q000493:pharmacokinetics / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D042967:Electron Transport Complex I; D003576:Electron Transport Complex IV / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D008928:Mitochondria / Q000201:enzymology*; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016716:PC12 Cells; D012333:RNA, Messenger / Q000032:analysis; D012335:RNA, Ribosomal / Q000235:genetics; D051381:Rats
D017607:Aluminum Compounds; D001252:Astringents; D002712:Chlorides; D012333:RNA, Messenger; D012335:RNA, Ribosomal; C075526:RNA, ribosomal, 12S; D000077410:Aluminum Chloride; D009247:NADH, NADPH Oxidoreductases; D003576:Electron Transport Complex IV; D042967:Electron Transport Complex I