Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II. Export

@article{citeulike:5717746, abstract = {In renal proximal tubule epithelial cells, a membrane-associated phospholipase A2 (PLA2) is a major signaling pathway linked to angiotensin II (Ang II) type 2 receptor (AT2). The current studies were designed to test the hypothesis that membrane-associated PLA2-induced release of arachidonic acid (AA) and/or its metabolites may serve as an upstream mediator of Ang II-induced mitogen-activated protein kinase (MAPK) activation. Ang II stimulated transient dose-dependent phosphorylation of MAPK with a maximum at 1 microM (10 min). Inhibition of PLA2 by mepacrine diminished both AA release and MAPK phosphorylation, induced by Ang II. Furthermore, AA itself induced time- and dose-dependent phosphorylation of MAPK, supporting the importance of PLA2 as a mediator of Ang II signaling. The effects of both Ang II and AA on MAPK phosphorylation were protein kinase C independent and abolished by the inhibitor of cytochrome P450 isoenzyme, ketoconazole. Moreover, 5,6-epoxyeicosatrienoic acid and 14,15-epoxyeicosatrienoic acid, the cytochrome P450-dependent metabolites of AA, significantly stimulated MAPK activity in renal proximal tubule epithelial cells. These observations document a mechanism of Ang II-induced MAPK phosphorylation, mediated by PLA2-dependent release of AA and cytochrome P450-dependent production of epoxy derivatives of AA.}, author = {Dulin, N. O. and Alexander, L. D. and Harwalkar, S. and Falck, J. R. and Douglas, J. G.}, citeulike-article-id = {5717746}, citeulike-linkout-0 = {http://view.ncbi.nlm.nih.gov/pubmed/9653146}, citeulike-linkout-1 = {http://www.hubmed.org/display.cgi?uids=9653146}, day = {7}, issn = {0027-8424}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {aa, aii, cyp, mapk, pla2}, month = {July}, number = {14}, pages = {8098--8102}, posted-at = {2009-09-03 13:34:38}, priority = {2}, title = {Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/9653146}, volume = {95}, year = {1998} }

TY - JOUR ID - citeulike:5717746 L3 - citeulike-article-id:5717746 N2 - In renal proximal tubule epithelial cells, a membrane-associated phospholipase A2 (PLA2) is a major signaling pathway linked to angiotensin II (Ang II) type 2 receptor (AT2). The current studies were designed to test the hypothesis that membrane-associated PLA2-induced release of arachidonic acid (AA) and/or its metabolites may serve as an upstream mediator of Ang II-induced mitogen-activated protein kinase (MAPK) activation. Ang II stimulated transient dose-dependent phosphorylation of MAPK with a maximum at 1 microM (10 min). Inhibition of PLA2 by mepacrine diminished both AA release and MAPK phosphorylation, induced by Ang II. Furthermore, AA itself induced time- and dose-dependent phosphorylation of MAPK, supporting the importance of PLA2 as a mediator of Ang II signaling. The effects of both Ang II and AA on MAPK phosphorylation were protein kinase C independent and abolished by the inhibitor of cytochrome P450 isoenzyme, ketoconazole. Moreover, 5,6-epoxyeicosatrienoic acid and 14,15-epoxyeicosatrienoic acid, the cytochrome P450-dependent metabolites of AA, significantly stimulated MAPK activity in renal proximal tubule epithelial cells. These observations document a mechanism of Ang II-induced MAPK phosphorylation, mediated by PLA2-dependent release of AA and cytochrome P450-dependent production of epoxy derivatives of AA. IS - 14 JF - Proceedings of the National Academy of Sciences of the United States of America SN - 0027-8424 EP - 8102 TI - Phospholipase A2-mediated activation of mitogen-activated protein kinase by angiotensin II. VL - 95 SP - 8098 KW - aa KW - aii KW - cyp KW - mapk KW - pla2 AU - Dulin, NO AU - Alexander, LD AU - Harwalkar, S AU - Falck, JR AU - Douglas, JG PY - 1998/07/07/ UR - http://view.ncbi.nlm.nih.gov/pubmed/9653146 ER -