Nitric oxide (NO) and p38 have been shown to be involved in the ischemia/hypoxia-induced neuronal injury. In this study, we examined the activation patterns of mitogen-activated protein kinases and explored the relationship between NO and p38 in a model of hippocampal neuronal death induced by hypoxia/reoxygenation (H/R). p38 activity increased robustly during hypoxia and after reoxygenation, while the increase of c-Jun amino-terminal kinase and extracellular signal-related kinase activities showed mild tendency. Inhibition of p38 with SB203580 or SB202190 rescued neuronal death, whereas inhibition of extracellular signal-related kinases with PD98059 or c-Jun amino-terminal kinases with SP600125 offered no protection. p38 inhibitors also reduced neuronal death induced by the NO donor S-nitrosoglutathione. L-NAME, a nonspecific NO synthase inhibitor, blocked the p38 activation and rescued H/R-induced neuronal death. These results suggest that NO is an upstream signal of p38 that mediates the H/R-induced neuronal death.
© 2009 S. Karger AG, Basel
- Hippocampal neuron
- Cell death
- Nitric oxide
- Mitogen-activated protein kinase
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Tian-Ming Gao, MD, PhD
Department of Anatomy and Neurobiology
Southern Medical University
Guangzhou 510515 (China)
Tel./Fax +86 20 6164 8216, E-Mail firstname.lastname@example.org
Received: April 22, 2008
Accepted after revision: June 24, 2008
Published online: March 4, 2009
Number of Print Pages : 7
Number of Figures : 5, Number of Tables : 0, Number of References : 26
Vol. 17, No. 2, Year 2009 (Cover Date: May 2009)
Journal Editor: Ip N.Y. (Hong Kong)
ISSN: 1424-862X (Print), eISSN: 1424-8638 (Online)
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