Astaxanthin protects against MPTP/MPP+-induced mitochondrial dysfunction and ROS production in vivo and in vitro.
Astaxanthin (AST) is a powerful antioxidant that occurs naturally in a wide variety of living organisms. We have investigated the role of AST in preventing 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced apoptosis of the substantia nigra (SN) neurons in the mouse model of Parkinson's disease (PD) and 1-methyl-4-phenylpyridinium (MPP+)-induced cytotoxicity of SH-SY5Y human neuroblastoma cells. In in vitro study, AST inhibits MPP+-induced production of intracellular reactive oxygen species (ROS) and cytotoxicity in SH-SY5Y human neuroblastoma cells. Preincubation of AST (50 μM) significantly attenuates MPP+-induced oxidative damage. Furthermore, AST is able to enhance the expression of Bcl-2 protein but reduce the expression of α-synuclein and Bax, and suppress the cleavage of caspase-3. Our results suggest that the protective effects of AST on MPP+-induced apoptosis may be due to its anti-oxidative properties and anti-apoptotic activity via induction of expression of superoxide dismutase (SOD) and catalase and regulating the expression of Bcl-2 and Bax. Pretreatment with AST (30 mg/kg) markedly increases tyrosine hydroxylase (TH)-positive neurons and decreases the argyrophilic neurons compared with the MPTP model group. In summary, AST shows protection from MPP+/MPTP-induced apoptosis in the SH-SY5Y cells and PD model mouse SN neurons, and this effect may be attributable to upregulation of the expression of Bcl-2 protein, downregulation of the expression of Bax and α-synuclein, and inhibition of the activation of caspase-3. These data indicate that AST may provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.
Department of Surgery, School of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.
Dae-Hee
DH
Lee
Cuk-Seong
CS
Kim
Yong J
YJ
Lee
D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000096:biosynthesis; D045744:Cell Line, Tumor; D003580:Cytochromes / Q000378:metabolism; D004789:Enzyme Activation; D004790:Enzyme Induction; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D066298:In Vitro Techniques; D020267:MPTP Poisoning / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D008807:Mice, Inbred BALB C; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis; D024341:Xanthophylls / Q000494:pharmacology
D000975:Antioxidants; D003580:Cytochromes; D017382:Reactive Oxygen Species; D024341:Xanthophylls; C005948:astaxanthine; D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3; D015655:1-Methyl-4-phenylpyridinium