Protein kinase C-independent pathway for NADPH oxidase activation in guinea pig peritoneal polymorphonuclear leukocytes by cytochalasin D.
Cytochalasin D (CD) induced production of the superoxide radical (O(2)(-)) in guinea pig polymorphonuclear leukocytes (PMNs). The protein kinase C (PKC) inhibitor GF109203X (GFX) was rarely without effect on CD-induced O(2)(-) production. CD as well as PMA induced the translocation of p47(phox) to the membrane fraction, and this translocation was slightly decreased by GFX. Moreover, the inhibitory effect of a PKCzeta antagonist with sequences based on the endogenous PKCzeta pseudosubstrate region was weaker than the inhibitory effect on N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced O(2)(-) production. On the other hand, the production of O(2)(-) induced by CD was more strongly suppressed by the PLD inhibitor ethanol and phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin than that induced by fMLP, and the activation of phospholipase D (PLD) by CD was restrained by wortmannin. These findings suggest that NADPH oxidase is activated by CD through a PKC-independent signaling pathway in PMNs, and this pathway involves the activation of PLD through PI3-K.
Imagawa
Naoki
N
Department of Environmental Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Japan.
Nagasawa
Kazuki
K
Nagai
Katsuhito
K
Kawakami-Honda
Naoko
N
Fujimoto
Sadaki
S
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D015638:Cytochalasin D / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007211:Indoles / Q000494:pharmacology; D008301:Maleimides / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D019255:NADPH Oxidases / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology*; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010739:Phospholipase D / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D021381:Protein Transport; D011760:Pyrrolidinones / Q000494:pharmacology; D015398:Signal Transduction; D013347:Subcellular Fractions; D000077191:Wortmannin; D000099221:Protein Kinase C zeta
D000730:Androstadienes; D015638:Cytochalasin D; D004791:Enzyme Inhibitors; D004963:Estrenes; D000431:Ethanol; D007211:Indoles; D008301:Maleimides; D009240:N-Formylmethionine Leucyl-Phenylalanine; D019255:NADPH Oxidases; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010739:Phospholipase D; D010750:Phosphoproteins; D011493:Protein Kinase C; D011760:Pyrrolidinones; D000077191:Wortmannin; D000099221:Protein Kinase C zeta; C060229:1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione; C060505:neutrophil cytosolic factor 1; C070515:bisindolylmaleimide I