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

Suryanarayana Vepa, William M. Scribner, Narasimham L. Parinandi, Denis English, Joe G.N. Garcia, Viswanathan Natarajan

Research output: Contribution to journalArticle

129 Scopus citations

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 (p125(FAK)) 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 micro filament 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.

Original languageEnglish (US)
Pages (from-to)L150-L158
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Volume277
Issue number1 21-1
DOIs
StatePublished - Jul 1999

Keywords

  • Cytoskeleton
  • Oxidants
  • Signal transduction
  • Tyrosine kinase

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Physiology (medical)
  • Cell Biology

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