Neuroprotective effects of ugonin K on hydrogen peroxide-induced cell death in human neuroblastoma SH-SY5Y cells.

Abstract

Oxidative stress plays an important role in the pathological processes of various neurodegenerative diseases. Ugonin K, a flavonoid isolated from the rhizomes of Helminthostachys zeylanica, possesses potent antioxidant property. In this study, we investigate the neuroprotective effects of ugonin K on hydrogen peroxide (H(2)O(2))-induced apoptosis in SH-SY5Y cells. Incubation of SH-SY5Y cells with H(2)O(2) for 24 h induced cell death measured with MTT assay. Hoechst 33258 staining confirmed that the reduced cell viability by H(2)O(2) was due to apoptosis. In addition, H(2)O(2) increased the expression of 17-kDa cleaved fragment of caspase-3 which could be reversed by pretreatment with ugonin K. Pretreatment with ugonin K attenuated H(2)O(2)-induced cell death in a dose-dependent manner. Neuroprotective effect of ugonin K was abolished by ERK and PI3K inhibitors. Pretreatment with JNK kinase and p38 MAPK inhibitors had no effect on ugonin K-mediated protection against H(2)O(2)-induced apoptosis. Western blotting with anti-phospho-ERK1/2 and anti-phospho-Akt (pS473) antibodies showed that ugonin K increased both ERK1/2 and Akt phosphorylation. These results suggest that ugonin K by activation of ERK1/2 and PI3K/Akt signal pathways protects SH-SY5Y cells from H(2)O(2)-induced apoptosis.

• Authors: Yi-Chien Lin, Yaun-Chao Huang, Sheng-Chih Chen, Chih-Chuang Liaw, Sheng-Chu Kuo, Li-Jiau Huang, Po-Wu Gean
• Journal: Neurochemical research (Neurochem Res) Vol. 34 Issue 5 Pg. 923-30 (May 2009) ISSN: 1573-6903 [Electronic] United States
• PMID: 18841465 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Cytotoxins
• Drugs, Chinese Herbal
• Flavonoids
• Neuroprotective Agents
• ugonin K
• Hydrogen Peroxide
• Phosphatidylinositol 3-Kinases
• Mitogen-Activated Protein Kinase 9
• Proto-Oncogene Proteins c-akt
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• Mitogen-Activated Protein Kinase 8
• Caspase 3

Topics

• Apoptosis (drug effects)
• Caspase 3 (metabolism)
• Cell Line, Tumor
• Cytotoxins (pharmacology)
• Drugs, Chinese Herbal (pharmacology)
• Enzyme Activation
• Flavonoids (pharmacology)
• Humans
• Hydrogen Peroxide (pharmacology)
• Mitogen-Activated Protein Kinase 1 (physiology)
• Mitogen-Activated Protein Kinase 3 (physiology)
• Mitogen-Activated Protein Kinase 8 (physiology)
• Mitogen-Activated Protein Kinase 9 (physiology)
• Neuroblastoma
• Neuroprotective Agents (pharmacology)
• Phosphatidylinositol 3-Kinases (physiology)
• Proto-Oncogene Proteins c-akt (metabolism)