title: AngII induces transient phospholipase D activity in the H295R glomerulosa cell model.
abstract: In this report we demonstrate that in human adrenocortical carcinoma NCI H295R cells, a model for adrenal glomerulosa cells, PLD was activated both by AngII and protein kinase C (PKC)-activating phorbol 12-myristate 13-acetate (PMA). However, while PMA triggered sustained PLD activation, AngII induced transient PLD activation, in contrast to results in bovine glomerulosa cells in primary culture. Despite the transient effect of AngII on PLD activity, PLD-derived lipid signals were required for maximal AngII-elicited aldosterone secretion. AngII-induced PLD activation was inhibited by PKC inhibitors, but not by tyrosine kinase or calcium/calmodulin-dependent kinase inhibitors or a calmodulin antagonist. Both AngII- and PMA-stimulated PLD activity was enhanced by phosphoinositide 3-kinase (PI3K) inhibitors. Akt, a downstream protein kinase activated by the products of PI3K, was constitutively active in H295R cells, and this activity was blocked by PI3K inhibitors. These results suggested that in H295R adrenocortical carcinoma cells, AngII-induced PLD activation was promoted by PKC and inhibited by the constitutively active PI3K pathway.
authors.affiliation: Institute of Molecular Medicine and Genetics/CB-2803, Medical College of Georgia, 1120 15th Street, Augusta, GA 30912-2630, USA.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zheng
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Bollag
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology*
chemical_list: D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D013755:Tetradecanoylphorbol Acetate