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

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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.

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  1. Manxiang Li

    Present address: Department of Physiology, University of Maryland School of Medicine, Howard Hall 523D, 660 W. Redwood Street, Baltimore, MD, 21201, USA

Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD, USA

    Manxiang Li, Kuan-Rau Chiou & David A. Kass

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  1. Manxiang Li
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  2. Kuan-Rau Chiou
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  3. David A. Kass
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Correspondence to Manxiang Li.

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Li, M., Chiou, KR. & Kass, D. Shear stress inhibition of H2O2 induced p66Shc phosphorylation by ASK1–JNK inactivation in endothelium. Heart Vessels 22, 423–427 (2007). https://doi.org/10.1007/s00380-007-0994-9

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  • DOI: https://doi.org/10.1007/s00380-007-0994-9

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