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Angiotensin II-Induced Generation of Reactive Oxygen Species Is Regulated by a Phosphatidylinositol 3-Kinase/L-Type Calcium Channel Signaling Pathway
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  • Journal title : Journal of Life Science
  • Volume 25, Issue 2,  2015, pp.231-236
  • Publisher : Korean Society of Life Science
  • DOI : 10.5352/JLS.2015.25.2.231
 Title & Authors
Angiotensin II-Induced Generation of Reactive Oxygen Species Is Regulated by a Phosphatidylinositol 3-Kinase/L-Type Calcium Channel Signaling Pathway
Jin, Seo Yeon; Ha, Jung Min; Kim, Young Whan; Lee, Hye Sun; Bae, Sun Sik;
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Angiotensin II (AngII) is an essential hormone that affects vascular physiology. For example, stimulation of vascular smooth muscle cells (VSMCs) rapidly induces vasoconstriction and results in the up-regulation of blood pressure. Chronic stimulation of VSMCs with AngII also results in hypertrophy. In this study, we confirmed an involvement of phosphatidylinositol 3-kinase (PI3K)-dependent calcium mobilization in AngII-induced generation of reactive oxygen species (ROS). Stimulation of rat aortic smooth muscle cells (RASMCs) with AngII significantly induced the generation of ROS in a dose- and time-dependent manner. AngII-induced generation of ROS was completely abolished by pharmacological inhibition of PI3K (with LY294002), but inhibition of the ERK signaling pathway had no effect. AngII-induced calcium mobilization was completely blocked by inhibition of PI3K, whereas inhibition of the ERK signaling pathway by PD98059 was ineffective. Depletion of extracellular calcium or inhibition of the L-type calcium channel by nifedipine completely blocked AngII-induced calcium mobilization. Depletion of extracellular calcium by EGTA and incubation of RASMCs with calcium-free medium both significantly blocked AngII-induced ROS generation. Inhibition of the L-type calcium channel also significantly blocked AngII-induced ROS generation. These results suggest that AngII-induced ROS generation is regulated by calcium mobilization, which, in turn, is modulated by a PI3K/L-type calcium channel signaling pathway.
Angiotensin;L-type calcium channel;PI3K (phosphatidylinositol 3-kinase);ROS (reactive oxygen species);smooth muscle cell;
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