Involvement of c-Src in diperoxovanadate-induced endothelial cell barrier dysfunction

Shu Shi, Joe G.N. Garcia, Shukla Roy, Narasimham L. Parinandi, Viswanathan Natarajan

Research output: Contribution to journalArticlepeer-review

9 Scopus citations


Reactive oxygen species (ROS) generated by activated leukocytes play an important role in the disruption of endothelial cell (EC) integrity, leading to barrier dysfunction and pulmonary edema. Although ROS modulate cell signaling, information remains limited regarding the mechanism(s) of ROS-induced EC barrier dysfunction. We utilized diperoxovanadate (DPV) as a model agent to explore the role of tyrosine phosphorylation in the regulation of EC barrier function. DPV disrupted EC barrier function in a dose-dependent manner. Tyrosine kinase inhibitors, genistein, and PP-2, a specific inhibitor of Src, reduced the DPV-mediated barrier dysfunction. Consistent with these results, DPV-induced Src activation was attenuated by PP-2. Furthermore, DPV increased the association of Src with cortactin and myosin light chain kinase, indicating their potential role as cytoskeletal targets for Src. Transient over-expression of either wild-type Src or a constitutively active Src mutant potentiated the DPV-mediated decline in barrier dysfunction, whereas a dominant negative Src mutant attenuated the response. These studies provide the first direct evidence for Src involvement in DPV-induced EC barrier dysfunction.

Original languageEnglish (US)
Pages (from-to)L441-L451
JournalAmerican Journal of Physiology - Lung Cellular and Molecular Physiology
Issue number3 23-3
StatePublished - 2000


  • Non-receptor tyrosine kinases
  • Tyrosine phosphorylation
  • Vascular permeability

ASJC Scopus subject areas

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


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