Parkinson’s disease (PD) is a progressive, neurodegenerative disorder which involves the loss of dopaminergic neurons of the substantia nigra pars compacta. 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, mitochondrial dysfunction, and ultimately to subsequent neuronal cell death. Selective reductions in GSH levels which precede losses in mitochondrial complex I activity have been reported to occur not only in PD but also in associated toxin models of the disease such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. R-lipoic acid plays a fundamental role in mitochondrial metabolism as a coenzyme for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase and as a substrate for the NADPH-dependent enzyme glutathione reductase. To address the question of the possible mechanism of R-lipoic acid-mediated protection, we have investigated its effect on dopaminergic neurotoxin-treated SH-SY5Y cells. We have anlyzed the effect of MPP+ or rotenone and/or R-lipoic acid on viability, GSH levels, mitochondrial respiratory chain complex I activity and ATP production in human dopaminergic SH-SY5Y cells. We found that MPP+ and rotenone dose- and time- dependently altered SH-SY5Y cell viability associated with a decreased of GSH levels, complex I activity and ATP production. We observed a protective effect R-lipoic acid on SH-SY5Y cells against MPP+ and rotenone indicating this compound as potential agent in prevention of neuronal degeneration in PD. Supported by the University of Bologna, Funds for Selected Research Topics.
R-lipoic acid-mediated neuroprotection against cellular insults to human dopaminergic neurons
DOZZA, BARBARA;STROCCHI, PAOLA
2005
Abstract
Parkinson’s disease (PD) is a progressive, neurodegenerative disorder which involves the loss of dopaminergic neurons of the substantia nigra pars compacta. 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, mitochondrial dysfunction, and ultimately to subsequent neuronal cell death. Selective reductions in GSH levels which precede losses in mitochondrial complex I activity have been reported to occur not only in PD but also in associated toxin models of the disease such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration. R-lipoic acid plays a fundamental role in mitochondrial metabolism as a coenzyme for pyruvate dehydrogenase and alpha-ketoglutarate dehydrogenase and as a substrate for the NADPH-dependent enzyme glutathione reductase. To address the question of the possible mechanism of R-lipoic acid-mediated protection, we have investigated its effect on dopaminergic neurotoxin-treated SH-SY5Y cells. We have anlyzed the effect of MPP+ or rotenone and/or R-lipoic acid on viability, GSH levels, mitochondrial respiratory chain complex I activity and ATP production in human dopaminergic SH-SY5Y cells. We found that MPP+ and rotenone dose- and time- dependently altered SH-SY5Y cell viability associated with a decreased of GSH levels, complex I activity and ATP production. We observed a protective effect R-lipoic acid on SH-SY5Y cells against MPP+ and rotenone indicating this compound as potential agent in prevention of neuronal degeneration in PD. Supported by the University of Bologna, Funds for Selected Research Topics.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
