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Implication of reduced levels of intracellular cAMP in enhanced expression of Gi proteins and hyperproliferation of vascular smooth muscle cells from spontaneously hypertensive rats: cellular mechanisms
Author(s) -
Gusan Svetlana,
Ananad-Srivastava Madhu
Publication year - 2012
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.26.1_supplement.666.2
Subject(s) - vascular smooth muscle , intracellular , endocrinology , signal transduction , medicine , angiotensin ii , cell growth , phosphorylation , chemistry , western blot , microbiology and biotechnology , downregulation and upregulation , biology , biochemistry , smooth muscle , gene , blood pressure
We earlier showed that vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR) exhibited an increased expression of Gi proteins and hyperproliferation, whereas the levels of cAMP were decreased as compared to WKY control rats. The enhanced levels of endogenous AngII and ET‐1 in VSMC from SHR were shown to contribute to the increased expression of Gi proteins through the transactivation of EGFR and MAP kinase signaling pathways. The present study was undertaken to examine if the decreased levels of intracellular cAMP in VSMC from SHR contribute to the enhanced expression of Gi proteins and hyperproliferation and to explore the underlying signaling pathways. Protein expression was evaluated by Western blot analysis and cell proliferation by thymidine incorporation. Treatment of VSMC from SHR with dbcAMP attenuated the enhanced expression of Gi proteins and the enhanced proliferation to control levels. In addition, the increased phosphorylation of ERK1/2, c‐Src, EGFR and PDGFR in VSMC from SHR was also inhibited by dbcAMP. Furthermore, dbcAMP decreased the enhanced production of superoxide anion and enhanced expression of Nox4, p47 proteins. These results suggest that the decreased levels of intracellular cAMP in VSMC from SHR contribute to the enhanced expression of Gi protein and proliferation through ROS‐mediated EGFR/PDGFR activation and ERK1/2 signaling pathway (Supported by CIHR).