Dopamine oxidation products inhibit Na+, K+-ATPase activity in crude synaptosomal-mitochondrial fraction from rat brain.
The diverse damaging effects of dopamine (DA) oxidation products on brain subcellular components including mitochondrial electron transport chain have been implicated in dopaminergic neuronal death in Parkinson's disease. It has been shown in this study that DA (50-200 microM) causes dose-dependent inhibition of Na+, K+-ATPase activity of rat brain crude synaptosomal-mitochondrial fraction during in vitro incubation up to 2 h. The enzyme inactivation is prevented by catalase and the metal-chelator (diethylenetriamine penta-acetic acid) but not by superoxide dismutase or hydroxyl-radical scavengers like mannitol and dimethylsulphoxide (DMSO). Further, reduced glutathione and cysteine, markedly prevent DA-mediated inactivation of Na+, K+-ATPase. Under similar conditions of incubation, DA (200 microM) leads to the formation of quinoprotein adducts (protein-cysteinyl catechol) with synaptosomal-mitochondrial proteins and the phenomenon is also prevented by glutathione (5 mM) or cysteine (5 mM). The available data imply that the inactivation of Na+, K+-ATPase in this system involves both H2O2 and metal ions. The reactive quinones by forming adducts with protein thiols also probably contribute to the process, since reduced glutathione and cysteine which scavenge quinones from the system protect Na+, K+-ATPase from DA-mediated damage. The inactivation of neuronal Na+, K+-ATPase by DA may give rise to various toxic sequelae with potential implications for dopaminergic cell death in Parkinson's disease.
Khan
Firoj Hossain
FH
Department of Biochemistry, University College of Medicine, Calcutta University, 244B, A.J.C. Bose Road, Calcutta 020, India.
Sen
Tanusree
T
Chakrabarti
Sasanka
S
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002614:Chelating Agents / Q000494:pharmacology; D003545:Cysteine / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000201:enzymology / Q000378:metabolism*; D013997:Time Factors
D002614:Chelating Agents; D004791:Enzyme Inhibitors; D002374:Catalase; D000254:Sodium-Potassium-Exchanging ATPase; D005978:Glutathione; D003545:Cysteine; D010100:Oxygen; D004298:Dopamine; D004121:Dimethyl Sulfoxide