Hydrogen peroxide stimulates tyrosine phosphorylation of focal adhesion kinase in vascular endothelial cells

Abstract

Reactive oxygen species (ROS) are implicated in the pathophysiology of several vascular disorders including atherosclerosis. Although the mechanism(s) of ROS-induced vascular damage remains unclear, there is increasing evidence for ROS-mediated modulation of signal transduction pathways. Exposure of bovine pulmonary artery endothelial cells to hydrogen peroxide (H2O2) enhanced tyrosine phosphorylation of 60- to 80- and 110- to 130-kDa cellular proteins, which were determined by immunoprecipitation with specific antibodies focal adhesion kinase (p125FAK) and paxillin (p68). Brief exposure of cells to a relatively high concentration of H2O2(1 mM) resulted in a time- and dose-dependent tyrosine phosphorylation of FAK, which reached maximum levels within 10 min (290% of basal levels). Cytoskeletal reorganization as evidenced by the appearance of actin stress fibers preceded H2O2-induced tyrosine phosphorylation of FAK, and the microfilament disruptor cytochalasin D also attenuated the tyrosine phosphorylation of FAK. Treatment of BPAECs with 1,2-bis(2-aminophenoxy)ethane- N, N, N′, N′-tetraacetic acid-AM attenuated H2O2-induced increases in intracellular Ca2+but did not show any consistent effect on H2O2-induced tyrosine phosphorylation of FAK. Several tyrosine kinase inhibitors, including genistein, herbimycin, and tyrphostin, had no detectable effect on tyrosine phosphorylation of FAK but attenuated the H2O2-induction of mitogen-activated protein kinase activity. We conclude that H2O2-induced increases in FAK tyrosine phosphorylation may be important in H2O2-mediated endothelial cell activation.

Mn‐SOD antisense upregulates in vivo apoptosis of squamous cell carcinoma cells by anticancer drugs and γ‐rays regulating expression of the BCL‐2 family proteins, COX‐2 and p21

“…[1][2][3] However, ROIs have cell function-suppressing activities and impair cells, finally promoting malignant transformation. 4,5 To protect themselves from this impairment, cells possess defense systems against ROIs.…”

Oxidative Stress in Acute Coronary Syndrome

“…The increased production of ROS reduces the production and bioavailability of nitric oxide, leads to vasoconstriction, platelet aggregation and adhesion of neutrophils to the endothelium. [6,36] Atherosclerosis results due to oxidative modification of LDL in the arterial wall by ROS. Evidence suggests that common risk factors for atherosclerosis increase the risk of production of ROS.…”

Biochemical mechanisms underlying atherogenesis

“…28 Oxidative stress leading to increased hydrogen peroxide causes phosphorylation of tyrosine kinases, which leads to stronger binding of neutrophil cells on endothelium and alteration of vessel permeability. 29 The interaction of superoxide with NO leads to the production of peroxynitrite, a substance less effective for the activation of guanylate cyclase and reduced bioavailability of NO.…”