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Licensed Unlicensed Requires Authentication Published by De Gruyter June 1, 2005

Activation of c-Jun N-Terminal Kinase and Apoptosis in Endothelial Cells Mediated by Endogenous Generation of Hydrogen Peroxide

A. Ramachandran, D. Moellering, Y.-M. Go, S. Shiva, A.-L. Levonen, H. Jo, R.P. Patel, S. Parthasarathy and V.M. Darley-Usmar
From the journal


Reactive oxygen species have been implicated in the activation of signal transduction pathways. However, extracellular addition of oxidants such as hydrogen peroxide (H2O2) often requires concentrations that cannot be readily achieved under physiological conditions to activate biological responses such as apoptosis. Explanations for this discrepancy have included increased metabolism of H2O2 in the extracellular environment and compartmentalization within the cell. We have addressed this issue experimentally by examining the induction of apoptosis of endothelial cells induced by exogenous addition of H2O2 and by a redox cycling agent, 2,3-dimethoxy 1,4-naphthoquinone, that generates H2O2 in cells. Here we show that low nanomolar steadystate concentrations (0.1 0.5 nmolmin 1106 cells) of H2O2 generated intracellularly activate cJun N terminal kinase and initiate apoptosis in endothelial cells. A comparison with bolus hydrogen peroxide suggests that the low rate of intracellular formation of this reactive oxygen species results in a similar profile of activation for both cJun N terminal kinase and the initiation of apoptosis. However, a detailed analysis reveals important differences in both the duration and profile for activation of these signaling pathways.

Published Online: 2005-06-01
Published in Print: 2002-04-12

Copyright © 2002 by Walter de Gruyter GmbH & Co. KG

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