title: ERK and p38 MAP kinase are involved in arachidonic acid release induced by H(2)O(2) and PDGF in mesangial cells.
abstract: Increased prostaglandin production is implicated in the pathogenesis of glomerular disease. With this consideration, we examined the combined effects of reactive oxygen species and platelet-derived growth factor (PDGF), which might initiate glomerular dysfunction, on arachidonic acid release and cytosolic phospholipase A(2) (cPLA(2)) activation in rat mesangial cells. H(2)O(2)-induced release of arachidonic acid was enhanced by PDGF, which by itself had little effect on the release, and the enhancement was completely inhibited by a cPLA(2) inhibitor. The phosphorylation of cPLA(2), extracellular signal-regulated kinase (ERK), and p38 mitogen-activated protein (MAP) kinase was upregulated by H(2)O(2) or PDGF alone and except for ERK was enhanced further by the two in combination. The release of arachidonic acid induced by PDGF together with H(2)O(2) was inhibited partially by an inhibitor of ERK or p38 MAP kinase and completely when the two inhibitors were combined; the inhibitory pattern was similar to that for the phosphorylation of cPLA(2). These results suggest that the ERK and p38 MAP kinase pathways are involved in the increase in cPLA(2) activation and arachidonic acid release induced by PDGF together with H(2)O(2).
authors.affiliation: Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Hayama
authors.forename: Risa
authors.initials: R
authors.lastname: Inoue
authors.forename: Satoshi
authors.initials: S
authors.lastname: Akiba
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000493:pharmacokinetics*; D000077214:Becaplermin; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D005920:Glomerular Mesangium / Q000166:cytology / Q000201:enzymology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016877:Oxidants / Q000494:pharmacology; D010741:Phospholipases A / Q000378:metabolism; D010766:Phosphorylation; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D000925:Anticoagulants; D004791:Enzyme Inhibitors; D005419:Flavonoids; D007093:Imidazoles; D016877:Oxidants; D010982:Platelet-Derived Growth Factor; D020574:Proto-Oncogene Proteins c-sis; D011725:Pyridines; D014316:Tritium; D000077214:Becaplermin; D016718:Arachidonic Acid; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D010741:Phospholipases A; C090942:4-(4-fluorophenyl)-2-(4-hydroxyphenyl)-5-(4-pyridyl)imidazole; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one