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Hydrogen peroxide (H 2 O 2 ) increased the expression of Gqα in vascular smooth muscle cells: role of growth factor receptors
Author(s) -
Descorbeth Magda,
AnandSrivastava Madhu B.
Publication year - 2008
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.22.1_supplement.908.14
Subject(s) - wortmannin , vascular smooth muscle , receptor , mapk/erk pathway , growth factor , platelet derived growth factor receptor , gq alpha subunit , transactivation , phosphatidylinositol , signal transduction , microbiology and biotechnology , chemistry , protein kinase a , endocrinology , medicine , kinase , biology , g protein , biochemistry , gene expression , smooth muscle , gene
We have recently shown that high glucose increased the expressions of Gqα which was attributed to the enhanced levels of H 2 O 2 . The present studies were undertaken to investigate if H 2 O 2 can mimic the effect of high glucose on the expression of Gqα and‐mediated signaling in A10 VSMC. Treatment of A10 VSMC with H 2 O 2 for 4 h increased the levels of Gqα protein in a concentration‐dependent manner. A maximal increase of ~50% in the levels of Gqα proteins was observed at 50μM of H 2 O 2 . Since H 2 O 2 transactivates growth factor receptors, we also investigated the implication of growth factor receptors in H 2 O 2 ‐mediated increase in Gqα levels by using specifics inhibitors of growth factor receptors such as AG1024 for IGF‐R or AG1295 for PDGF‐R. Pretreatment of cells with growth factor receptor inhibitors resulted in the restoration of H 2 O 2 ‐induced enhanced expression of Gqα proteins. In addition, PD‐98059, an inhibitor of mitogen‐activated protein kinase (MAPK), and wortmannin, an inhibitor of phosphatidylinositol 3‐kinase (PI3‐K), decreased H 2 O 2 –induced enhanced levels of Gqα. On the other hand, the enhanced activity of MAPK induced by H 2 O 2 was also inhibited by growth factor receptors inhibitors. These results suggest that H 2 O 2 ‐mediated up‐regulation of Gqα expression in VSMC occurs through the transactivation of growth factor receptor‐induced activation of the MAPK/PI3K pathways. (Supported by Quebec Heart Foundation)