Premium
Early growth response protein‐1 (Egr‐1) expression by hydrogen peroxide (H 2 O 2 ) is mediated via c‐Src and PKB‐dependent CREB signaling events in vascular smooth muscle cells (VSMC)
Author(s) -
Truong Vanessa,
Rondeau Vincent,
Jain Ashish,
Srivastava Ashok K.
Publication year - 2018
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.2018.32.1_supplement.533.92
Subject(s) - phosphorylation , creb , vascular smooth muscle , wortmannin , protein kinase b , proto oncogene tyrosine protein kinase src , chemistry , signal transduction , microbiology and biotechnology , gene silencing , growth factor , pi3k/akt/mtor pathway , reactive oxygen species , transcription factor , medicine , endocrinology , biology , receptor , biochemistry , smooth muscle , gene
Increased generation of reactive oxygen species (ROS) is believed to play a key role in the pathophysiology of cardiovascular diseases. Excessive growth and proliferation of vascular smooth muscle cells (VSMC) have been suggested to be major contributors to vascular dysfunction. A potential involvement of early growth response protein‐1 (Egr‐1), a zinc‐finger transcription factor, in the development of vascular injury has been suggested. Recent studies have shown that H 2 O 2 , one of the most stable ROS, increases Egr‐1 expression in VSMC, however, signaling events leading to H 2 O 2 ‐induced Egr‐1 expression are not fully understood. Here, we report that H 2 O 2 increased Egr‐1 expression in a time and dose‐dependent fashion in A10 VSMC and pharmacological blockade of insulin‐like growth factor‐1 receptor (IGF‐1R) and c‐Src, by AG1024 and PP2 respectively, abolished H 2 O 2 ‐induced Egr‐1 expression while AG1478, an inhibitor of the epidermal growth factor receptor (EGFR), and PP3, the inactive analog of PP2, had no effect. H 2 O 2 also stimulated the phosphorylation of PKB, and siRNA‐induced silencing of c‐Src resulted in a significant reduction in PKB phosphorylation as well Egr‐1 expression. In addition, phosphorylation of cyclic AMP response element binding protein (CREB) was also enhanced by H 2 O 2, however, inhibition of PI3K/PKB by wortmannin and SC‐66 attenuated this phosphorylation, as well as suppressed protein and mRNA levels of Egr‐1 induced by H 2 O. In summary, our data suggests that H 2 O 2 provokes Egr‐1 expression through the activation of upstream tyrosine kinases IGF‐1R and c‐Src as well as PKB and CREB‐dependent signaling events in VSMC. Support or Funding Information (Supported by CIHR) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .