Quinone and oxyradical scavenging properties of N-acetylcysteine prevent dopamine mediated inhibition of Na+, K+-ATPase and mitochondrial electron transport chain activity in rat brain: implications in the neuroprotective therapy of Parkinson's disease.
Dopamine oxidation products such as H2O2 and reactive quinones have been held responsible for various toxic actions of dopamine, which have implications in the aetiopathogenesis of Parkinson's disease. This study has shown that N-acetylcysteine (0.25-1 mm) is a potent scavenger of both H2O2 and toxic quinones derived from dopamine and it further prevents dopamine mediated inhibition of Na+,K+-ATPase activity and mitochondrial respiratory chain function. The quinone scavenging ability of N-acetylcysteine is presumably related to its protective effect against dopamine mediated inhibition of mitochondrial respiratory chain activity. However, both H2O2 scavenging and quinone scavenging properties of N-acetylcysteine probably account for its protective effect against Na+,K+-ATPase inhibition induced by dopamine. The results have important implications in the neuroprotective therapy of sporadic Parkinson's disease since inactivation of mitochondrial respiratory activity and Na+,K+-ATPase may trigger intracellular damage pathways leading to the death of nigral dopaminergic neurons.
Bagh
Maria B
MB
Department of Biochemistry, Institute of Post Graduate Medical Education & Research, Dr B. C. Roy Post Graduate Institute of Basic Medical Sciences, India.
Maiti
Arpan K
AK
Jana
Sirsendu
S
Banerjee
Kalpita
K
Roy
Arun
A
Chakrabarti
Sasanka
S
D000111:Acetylcysteine / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D016227:Benzoquinones / Q000737:chemistry*; D001921:Brain / Q000378:metabolism*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology; D051381:Rats; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry / Q000502:physiology*
D016227:Benzoquinones; D016166:Free Radical Scavengers; D005609:Free Radicals; C004532:quinone; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D000254:Sodium-Potassium-Exchanging ATPase; D004298:Dopamine; D000111:Acetylcysteine