The role of p38 MAPK in valproic acid induced microglia apoptosis.

Abstract

Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, induces apoptosis in microglia, but the underlying mechanism by which microglia apoptosis in response to VPA is not yet known. In this study, we found that the mitochondrial pathway played an important role in VPA-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. In addition, VPA increased the level of phospho-p38 mitogen-activated protein kinase (MAPK), but had no effects on phospho-ERK and phospho-JNK MAPKs. Moreover, p38 inhibitor SB203580 strongly inhibited VPA-induced apoptosis and caspase-3 activation. Taken together, our results clearly demonstrated that VPA could induce apoptosis of microglia via p38 MAPK and mitochondrial apoptosis pathway.

• Authors: Nanchang Xie, Cui Wang, Youting Lin, Hui Li, Lin Chen, Tongxia Zhang, Yong Sun, Yi Zhang, Deling Yin, Zhaofu Chi
• Journal: Neuroscience letters (Neurosci Lett) Vol. 482 Issue 1 Pg. 51-6 (Sep 20 2010) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 20621161 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anticonvulsants
• Valproic Acid
• p38 Mitogen-Activated Protein Kinases

Topics

• Animals
• Anticonvulsants (pharmacology)
• Apoptosis (drug effects)
• Blotting, Western
• Cell Line
• Humans
• In Situ Nick-End Labeling
• Mice
• Mice, Inbred BALB C
• Microglia (drug effects, enzymology, pathology)
• Valproic Acid (pharmacology)
• p38 Mitogen-Activated Protein Kinases (drug effects, metabolism)