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Activation of c-Jun N-terminal kinase and apoptosis in endothelial cells mediated by endogenous generation of hydrogen peroxideReactive 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 steady-state concentrations (0.1-0.5 nmol x min(-1) x 10(6) cells) of H2O2 generated intracellularly activate c-Jun 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 c-Jun 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.
Document ID
20040088289
Acquisition Source
Legacy CDMS
Document Type
Reprint (Version printed in journal)
External Source(s)
Authors
Ramachandran, Anup
(University of Alabama at Birmingham 35294, United States)
Moellering, Douglas
Go, Young-Mi
Shiva, Sruti
Levonen, Anna-Liisa
Jo, Hanjoong
Patel, Rakesh P.
Parthasarathy, Sampath
Darley-Usmar, Victor M.
Date Acquired
August 21, 2013
Publication Date
March 1, 2002
Publication Information
Publication: Biological chemistry
Volume: 383
Issue: 4-Mar
ISSN: 1431-6730
Subject Category
Life Sciences (General)
Funding Number(s)
CONTRACT_GRANT: HL60905
CONTRACT_GRANT: HL58031
Distribution Limits
Public
Copyright
Other
Keywords
Non-NASA Center
NASA Discipline Cell Biology

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