Superoxide-mediated actin response in post-hypoxic endothelial cells

Lawrence E. Crawford, Emily E. Milliken, Kaikobad Irani, Jay L. Zweier, Lewis C. Becker, Thomas M. Johnson, N. Tony Eissa, Ronald G. Crystal, Toren Finkel, Pascal Goldschmidt-Clermont

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Abstract

The mechanism leading to changes in the superstructure of endothelial cells exposed to ischemia and reperfusion remains uncharacterized. We show that in posthypoxic endothelial cells, the simple re-addition of oxygen induces a profound reorganization of the actin cytoskeleton. The total filamentous actin pool increases by 41% and translocation of actin filaments to the submembranous network is observed. Concurrent with the actin polymerization, increased tyrosine phosphorylation of endothelial cell substrates is detected on Western blots. Overexpression of superoxide dismutase using replication incompetent adenovirus inhibits the actin and tyrosine phosphorylation responses to reoxygenation. Inhibition of tyrosine kinases with the isoflavone genistein also suppressed the actin polymerization response to reoxygenation, but unlike superoxide dismutase, genistein also induced the collapse of the superstructure of endothelial cells upon reoxygenation. These experiments support the concept that reoxygenation following a period of hypoxia can induce the remodeling of the actin cytoskeleton in endothelial cells. Such a response requires the intact coupling of superoxide producing pathway(s) with tyrosine kinase pathway(s).

Original languageEnglish
Pages (from-to)26863-26867
Number of pages5
JournalJournal of Biological Chemistry
Volume271
Issue number43
DOIs
StatePublished - Nov 6 1996
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Crawford, L. E., Milliken, E. E., Irani, K., Zweier, J. L., Becker, L. C., Johnson, T. M., Tony Eissa, N., Crystal, R. G., Finkel, T., & Goldschmidt-Clermont, P. (1996). Superoxide-mediated actin response in post-hypoxic endothelial cells. Journal of Biological Chemistry, 271(43), 26863-26867. https://doi.org/10.1074/jbc.271.43.26863