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Hydrogen Peroxide Enhances the Expression of Gi Protein in Aortic Vascular Smooth Muscle Cells : Relationship with Adenylyl Cyclase
Author(s) -
Mbong Nathan,
AnandSrivastava Madhu
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.962.3
Subject(s) - adenylyl cyclase , chemistry , kinase , vascular smooth muscle , protein kinase b , protein kinase a , signal transduction , reactive oxygen species , medicine , endocrinology , angiotensin ii , microbiology and biotechnology , biochemistry , biology , receptor , smooth muscle
Reactive oxygen species (ROS) play a critical role in the pathogenesis of many diseases including hypertension, atherosclerosis, and diabetes. We have recently shown that ROS contribute to enhanced expression of G i α protein in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). The current study was undertaken to investigate the effect of H 2 O 2 , an experimental mimicker of oxidative stress, on G i α protein expression and the implication of extracellular signal‐regulated kinase (ERK1/2), and phosphatidylinositol‐3 kinase (PI3K) signaling in H 2 O 2 ‐induced altered expression of G i α protein. Aortic VSMC were treated with different concentrations of H 2 O 2 (50 μM to 250 μM) for different periods of time (30 min to 4 hr). The protein expression was determined by Western Blotting using specific antibodies. H 2 O 2 enhanced the expression of G i α in a concentration and time‐dependent manner with a maximum increase at 100μM for 1hr, whereas G s α expression remained unchanged. The enhanced expression of G i α was demonstrated by the increased inhibition of adenylyl cyclase by inhibitory hormones such as angiotensin II, oxotremorine, and C‐ANP 4–23 . We also found that H 2 O 2 induced the phosphorylation of the serine/threonine kinases ERK1/2, and AKT/PKB (protein kinase B). Moreover, MEK, and PI3K inhibitors restored the H 2 O 2 –induced enhanced expression of G i α proteins to control levels, suggesting the implication of these proteins kinases in the enhanced level of G i α. In conclusion, the modulation of Gi protein expression by H 2 O 2 in aortic vascular smooth muscle cells involves the ERK1/2, and PI3K signaling pathways. This study was supported by the Canadian Institutes of Health Research grant