Sphingosine inhibition of NADPH oxidase activation in a cell-free system.
The effects of sphingoid bases, sphingosine and dihydrosphingosine, which are protein kinase C (PKC) inhibitors, on NADPH oxidase were examined in a cell-free system. The bases inhibited cell-free activation of NADPH oxidase by arachidonic acid at lower concentration than N-acetylsphingosine. Thus, positive charge in the molecules may play a critical role in inhibition of the oxidase. Sphingosine did not change the Km value for NADPH, but shifted the optimum concentration of arachidonic acid for activation of the oxidase. Moreover, sphingosine suppressed the translocation of p47-phox, one of the cytosolic components of the oxidase, to the membrane fraction, suggesting that the base inhibits the assembly of the components.
Sasaki
J I
JI
Department of Physiological Chemistry, Hiroshima University School of Medicine.
Yamaguchi
M
M
Saeki
S
S
Yamane
H
H
Okamura
N
N
Ishibashi
S
S
D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002474:Cell-Free System / Q000201:enzymology; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009504:Neutrophils / Q000201:enzymology; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D013481:Superoxides / Q000378:metabolism
D010750:Phosphoproteins; D013481:Superoxides; D016718:Arachidonic Acid; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1; D011493:Protein Kinase C; D013110:Sphingosine; C005682:safingol