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Journal of Biochemistry Advance Access published online on October 8, 2006
Journal of Biochemistry, doi:10.1093/jb/mvj204
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© 2006 The Japanese Biochemical Society.
Received September 4, 2006
Accepted September 29, 2006

Regular Paper

Involvement of p38 MAP Kinase in Not Only Activation of the Phagocyte NADPH Oxidase Induced by Formyl-methionyl-leucyl-phenylalanine but Also Determination of the Extent of the Activity

Kei Sakamoto 1, Futoshi Kuribayashi 2 *, Michio Nakamura 3, and Koichiro Takeshige 1

1 Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan
2 Department of Molecular and Cellular Biochemistry, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-ku, Fukuoka 812-8582, Japan; Department of Host-defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan
3 Department of Host-defense Biochemistry, Institute of Tropical Medicine, Nagasaki University, 1-12-4, Sakamoto, Nagasaki 852-8523, Japan

* To whom correspondence should be addressed.
Futoshi Kuribayashi, E-mail: kurikuri{at}net.nagasaki-u.ac.jp


  Abstract

Activated NADPH oxidase in neutrophils produces superoxide. We investigated the role of p38 MAP kinase in activating NADPH oxidase stimulated by the bacteria-derived peptide fMLP. fMLP-stimulated superoxide production was completely abolished by SB203580, a p38 MAP kinase inhibitor, whereas anisomycin, a p38 MAP kinase activator, did not induce superoxide production, indicating that p38 MAP kinase was essential, but not sufficient, for NADPH oxidase activation. Anisomycin pretreatment strongly activated p38 MAP kinase in fMLP-stimulated cells, accompanied by greatly increased superoxide production, suggesting that p38 MAP kinase determines the extent of the fMLP-stimulated NADPH oxidase activity. Furthermore, superoxide production was remarkably reactivated by cytochalasin B addition after fMLP-stimulated production had disappeared, and this was correlated with highly activated p38 MAP kinase. These results suggest that p38 MAP kinase is involved not only in activating NADPH oxidase stimulated by fMLP but also in determining the extent of its activity.

Keywords: fMLP; neutrophil; p38 MAPK; phagocyte NADPH oxidase; superoxide.
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