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KMID : 0613820150250020231
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Journal of Life Science
2015 Volume.25 No. 2 p.231 ~ p.236
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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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Jin Seo-Yeon
Ha Jung-Min
Kim Young-Whan
Lee Hye-Sun
Bae Sun-Sik
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Abstract
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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.
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KEYWORD
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Angiotensin, L-type calcium channel, PI3K (phosphatidylinositol 3-kinase), ROS (reactive oxygen species), smooth muscle cell
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