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Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells.
J Neurochem. 2008 Dec; 107(6):1730-40.JN

Abstract

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.

Authors+Show Affiliations

Research Team for Molecular Biomarkers, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19014378

Citation

Ikeda, Yasutaka, et al. "Protective Effects of Astaxanthin On 6-hydroxydopamine-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells." Journal of Neurochemistry, vol. 107, no. 6, 2008, pp. 1730-40.
Ikeda Y, Tsuji S, Satoh A, et al. Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. J Neurochem. 2008;107(6):1730-40.
Ikeda, Y., Tsuji, S., Satoh, A., Ishikura, M., Shirasawa, T., & Shimizu, T. (2008). Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. Journal of Neurochemistry, 107(6), 1730-40. https://doi.org/10.1111/j.1471-4159.2008.05743.x
Ikeda Y, et al. Protective Effects of Astaxanthin On 6-hydroxydopamine-induced Apoptosis in Human Neuroblastoma SH-SY5Y Cells. J Neurochem. 2008;107(6):1730-40. PubMed PMID: 19014378.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Protective effects of astaxanthin on 6-hydroxydopamine-induced apoptosis in human neuroblastoma SH-SY5Y cells. AU - Ikeda,Yasutaka, AU - Tsuji,Shinji, AU - Satoh,Akira, AU - Ishikura,Masaharu, AU - Shirasawa,Takuji, AU - Shimizu,Takahiko, Y1 - 2008/11/07/ PY - 2008/11/19/pubmed PY - 2009/4/10/medline PY - 2008/11/19/entrez SP - 1730 EP - 40 JF - Journal of neurochemistry JO - J Neurochem VL - 107 IS - 6 N2 - 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. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/19014378/Protective_effects_of_astaxanthin_on_6_hydroxydopamine_induced_apoptosis_in_human_neuroblastoma_SH_SY5Y_cells_ L2 - https://doi.org/10.1111/j.1471-4159.2008.05743.x DB - PRIME DP - Unbound Medicine ER -