TY - JOUR
T1 - Relationship between p38 mitogen-activated protein kinase and small GTPase Rac for the activation of NADPH oxidase in bovine neutrophils
AU - Yamamori, Tohru
AU - Inanami, Osamu
AU - Sumimoto, Hideki
AU - Akasaki, Takashi
AU - Nagahata, Hajime
AU - Kuwabara, Mikinori
N1 - Funding Information:
We thank Dr. H. Nakatsuji (Laboratory of Ecological Animal Agriculture, Experimental Farm, Faculty of Agriculture, Hokkaido University) and K. Waki for helpful support in the collection of bovine peripheral blood. This work was supported, in part, by Grants-in-Aid for Basic Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan (No. 12034203 [O.I.], No. 12660266 [O.I.] and No. 12460135 [M.K.]), by Grants-in-Aid to Cooperative Research in the Rakuno Gakuen University, and by grants for the project study “Epidemiology, Pathogenesis, and Control of Bovine Mastitis,” the Ministry of Agriculture, Forestry, and Fisheries of Japan.
PY - 2002
Y1 - 2002
N2 - Superoxide production by NADPH oxidase is essential for bactericidal properties of neutrophils. However, molecular mechanisms underlying the activation of this enzyme remain largely unknown. Here, using bovine neutrophils we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the signaling pathways of the NADPH oxidase activation. Superoxide production was induced by stimulation with serum-opsonized zymosan (OZ) and attenuated by p38 MAPK inhibitor, SB203580. OZ stimulation induced the translocation of p47phox and Rac to the plasma membrane and SB203580 completely blocked the translocation of Rac, but only partially blocked that of p47phox. Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this protein. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, blocked not only p38 MAPK activation but also Rac activation. However, SB203580 showed no effect on the PI3K activity. These results suggested that PI3K/p38 MAPK/Rac pathway was present in the activation of NADPH oxidase in bovine neutrophils.
AB - Superoxide production by NADPH oxidase is essential for bactericidal properties of neutrophils. However, molecular mechanisms underlying the activation of this enzyme remain largely unknown. Here, using bovine neutrophils we examined the role of p38 mitogen-activated protein kinase (p38 MAPK) in the signaling pathways of the NADPH oxidase activation. Superoxide production was induced by stimulation with serum-opsonized zymosan (OZ) and attenuated by p38 MAPK inhibitor, SB203580. OZ stimulation induced the translocation of p47phox and Rac to the plasma membrane and SB203580 completely blocked the translocation of Rac, but only partially blocked that of p47phox. Furthermore, SB203580 abolished the OZ-elicited activation of Rac, which was assessed by detecting the GTP-bound form of this protein. Phosphatidylinositol 3-kinase (PI3K) inhibitors, wortmannin and LY294002, blocked not only p38 MAPK activation but also Rac activation. However, SB203580 showed no effect on the PI3K activity. These results suggested that PI3K/p38 MAPK/Rac pathway was present in the activation of NADPH oxidase in bovine neutrophils.
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U2 - 10.1016/S0006-291X(02)00418-7
DO - 10.1016/S0006-291X(02)00418-7
M3 - Article
C2 - 12054696
AN - SCOPUS:0036076064
SN - 0006-291X
VL - 293
SP - 1571
EP - 1578
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 5
ER -