Shear stress inhibition of H2O2 induced p66Shc phosphorylation by ASK1-JNK inactivation in endothelium

Manxiang Li, Kuan Rau Chiou, David A. Kass

Research output: Contribution to journalArticlepeer-review

Abstract

Shear stress protects endothelium from a variety of risk factors for vascular disease. Here, we demonstrate a novel mechanism whereby shear stress inhibited reactive oxygen species (ROS)-triggered signaling cascades in endothelial cells. Stimulation of bovine aortic endothelial cells (BAECs) with H2O2 induced a 3.07-fold increase in p66Shc phosphorylation. This response was fully blocked by pretreatment of cells with specific JNK but not p38 or ERK MAP kinase inhibitor. Further study showed that knocking down of apoptosis signal-regulating kinase 1 (ASK1) by siRNA transfection in cells dramatically inhibited phosphorylation of JNK and p66Shc elicited by H2O2. Pre-perfusion of BAECs cultured in silastic tubes with laminar flow generated by a servo-pump system for 30 min also significantly suppressed H2O2-induced phosphorylation of p66Shc. This was accompanied by quantitatively similar inhibition of ASK1 and JNK phosphorylation and activation. These results suggested that shear stress protects endothelium against oxidant stress by suppression of ASK1-JNK-mediated p66Shc phosphorylation.

Original languageEnglish (US)
Pages (from-to)423-427
Number of pages5
JournalHeart and Vessels
Volume22
Issue number6
DOIs
StatePublished - Nov 2007

Keywords

  • ASK1-JNK
  • Endothelium
  • Oxidant stress
  • Shear stress
  • p66

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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