Shear stress modulates expression of Cu/Zn superoxide dismutase in human aortic endothelial cells

Nobutaka Inoue, Santhini Ramasamy, Tohru Fukai, Robert M. Nerem, David G. Harrison

Research output: Contribution to journalArticle

232 Scopus citations

Abstract

A major determinant of the level of cellular superoxide anion (O2.) is the disputation of O2. to hydrogen peroxide by the enzyme superoxide dismutase (SOD). Three forms of SOD exist, but in endothelial cells, the major form outside of the mitochondria is the cytosolic copper/zinc- containing superozide dismutase (Cu/Zn SOD). Since fluid shear stress is an important determinant of the function and structure of endothelial cells in vivo, we examined the effect of laminar shear stress on the expression of Cu/Zn SOD in cultured human aortic endothelial cells. Laminar shear stress of 0.6 to 15 dyne/cm2 increased Cu/Zn SOD mRNA in a time- and dose-dependent manner in human aortic endothelial cells. Shear stress also increased both Cu/Zn SOD protection content and the enzyme activity. Nuclear run-on assays showed that nuclei from human aortic endothelial cells exposed to laminar shear stress had a 1.6-fold greater transcriptional activity of the Cu/Zn SOD gene compared with cells not exposed to shear, indicating that an increase in Cu/Zn SOD mRNA induced by laminar shear stress is at least in part mediated by increased transcription. In contrast, shear stress had no effect on Cu/Zn SOD mRNA levels in human aortic smooth muscle cells. These findings show that physiological levels of shear stress increase expression of Cu/Zn SOD in the endothelium. This adaptation to shear stress might augment the effect of locally produced NO. and thereby promote the antiatherogenic and antiinflammatory properties of the endothelial cell.

Original languageEnglish (US)
Pages (from-to)32-37
Number of pages6
JournalCirculation research
Volume79
Issue number1
DOIs
StatePublished - Jul 1996
Externally publishedYes

Keywords

  • endothelium
  • hemodynamics
  • shear stress
  • superoxide
  • superoxide dismutase

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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