Parkinson's disease (PD) is a
neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra pars compacta. Although understanding of the pathogenesis of PD remains incomplete, increasing evidence from human and animal studies has suggested that oxidative stress is an important mediator in its pathogenesis.
Astaxanthin (Asx), a potent
antioxidant, has been thought to provide health benefits by decreasing the risk of oxidative stress-related diseases. This study examined the protective effects of Asx on
6-hydroxydopamine (6-OHDA)-induced apoptosis in the human
neuroblastoma cell line SH-SY5Y. Pre-treatment of SH-SY5Y cells with Asx suppressed 6-OHDA-induced apoptosis in a dose-dependent manner. In addition, Asx strikingly inhibited 6-OHDA-induced
mitochondrial dysfunctions, including lowered membrane potential and the cleavage of
caspase 9,
caspase 3, and
poly(ADP-ribose) polymerase. In western blot analysis,
6-OHDA activated
p38 MAPK, c-jun NH(2)-terminal
kinase 1/2, and
extracellular signal-regulated kinase 1/2, while Asx blocked the phosphorylation of
p38 MAPK but not c-jun NH(2)-terminal
kinase 1/2 and
extracellular signal-regulated kinase 1/2. Pharmacological approaches showed that the activation of
p38 MAPK has a critical role in 6-OHDA-induced
mitochondrial dysfunctions and apoptosis. Furthermore, Asx markedly abolished 6-OHDA-induced
reactive oxygen species generation, which resulted in the blockade of
p38 MAPK activation and apoptosis induced by
6-OHDA treatment. Taken together, the present results indicated that the protective effects of Asx on apoptosis in SH-SY5Y cells may be, at least in part, attributable to the its potent antioxidative ability.