title: The effect of anionic amphiphiles on the recruitment of Rac in neutrophils.
abstract: Anionic amphiphiles have been shown to influence the NADPH oxidase system. Although one target of the amphiphile action is p47(phox), the cell-free activation of the enzyme in the absence of p47(phox) is also influenced. In the present study, we examined the actions of sodium dodecyl sulfate (SDS) on the NADPH oxidase system in vivo. Treatment of guinea pig neutrophils with the amphiphile caused the translocation of Rac to a membrane fraction and its conversion to the GTP-bound form. Because SDS had little effect on p47(phox), it increased the superoxide production only when p47(phox) was otherwise activated. Inhibitors of phosphoinositide 3-kinases had no effect on the SDS-induced translocation of Rac to the membrane. However, the inhibitors prevented the conversion of Rac to its GTP-bound form, indicating that these two processes can be controlled separately. In a cell-free system, SDS induced the binding of p47(phox) and Rac to the membrane preparation. The SDS concentration inducing the Rac binding was lower than that inducing the p47(phox) binding. Thus we observed that Rac is more sensitive to SDS than p47(phox) both in vivo and in vitro. The results suggest a role of natural amphiphiles such as unsaturated fatty acids in regulation of Rac activation.
authors.affiliation: Division of Molecular Medical Science, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8551, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Nigorikawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Okamura
authors.forename: Osamu
authors.initials: O
authors.lastname: Hazeki
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D000838:Anions; D016718:Arachidonic Acid / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002474:Cell-Free System; D002867:Chromones / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006160:Guanosine Triphosphate / Q000737:chemistry; D006168:Guinea Pigs; D046911:Macromolecular Substances / Q000494:pharmacology; D008387:Marine Toxins; D009025:Morpholines / Q000494:pharmacology; D019255:NADPH Oxidases / Q000737:chemistry* / Q000378:metabolism*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism*; D010080:Oxazoles / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D021381:Protein Transport; D011518:Proto-Oncogene Proteins / Q000502:physiology*; D051057:Proto-Oncogene Proteins c-akt; D012967:Sodium Dodecyl Sulfate / Q000737:chemistry / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D013501:Surface-Active Agents / Q000494:pharmacology*; D013997:Time Factors; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D000838:Anions; D016718:Arachidonic Acid; D002867:Chromones; D004791:Enzyme Inhibitors; D006160:Guanosine Triphosphate; D046911:Macromolecular Substances; D008387:Marine Toxins; D009025:Morpholines; D019255:NADPH Oxidases; D010080:Oxazoles; D010100:Oxygen; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D012967:Sodium Dodecyl Sulfate; D013481:Superoxides; D013501:Surface-Active Agents; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; C059041:calyculin A; C060505:neutrophil cytosolic factor 1