Pre-treatment with R-lipoic acid alleviates the effects of GSH depletion in PC12 cells: implications for Parkinson's disease therapy.
Oxidative stress is believed to play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) of Parkinson's disease (PD) patients. An important biochemical feature of PD is a significant early depletion in levels of the thiol antioxidant compound glutathione (GSH) which may lead to the generation of reactive oxygen species (ROS), mitochondrial dysfunction, and ultimately to subsequent neuronal cell death. In earlier work from our laboratory, we demonstrated that depletion of GSH in dopaminergic PC12 cells affects mitochondrial integrity and specifically impairs the activity of mitochondrial complex I. Here we report that pre-treatment of PC12 cells with R-lipoic acid acts to prevent depletion of GSH content and preserves the mitochondrial complex I activity which normally is impaired as a consequence of GSH loss.
Bharat
S
S
Buck Institute for Age Research, Novato, CA 94945, USA. bsrinivas@buckinstitute.org
Cochran
B C
BC
Hsu
M
M
Liu
J
J
Ames
B N
BN
Andersen
J K
JK
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000172:deficiency / Q000502:physiology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D016716:PC12 Cells; D010300:Parkinson Disease / Q000188:drug therapy*; D051381:Rats; D008063:Thioctic Acid / Q000627:therapeutic use*
D000975:Antioxidants; D019328:Buthionine Sulfoximine; D008063:Thioctic Acid; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione