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Title: p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis

Abstract

Doxorubicin is the anthracycline with the widest spectrum of antitumor activity, and it has been shown that the antitumor activity is mediated in vivo by selective triggering of apoptosis in proliferating endothelial cells. We studied cultured human endothelial cells and observed that doxorubicin-induced apoptosis was mediated by p38 mitogen-activated protein kinase (MAPK). Doxorubicin-provoked apoptosis was significantly inhibited by expression of dominant negative p38 MAPK or pharmacological inhibition with SB203580. Furthermore, blocking phosphatidylinositol-3-kinase/Akt signaling significantly increased doxorubicin-induced caspase-3 activity and cell death, indicating that Akt is a survival factor in this system. Notably, we also found that doxorubicin-provoked apoptosis included p38 MAPK-mediated inhibition of Akt and Bad phosphorylation. Furthermore, doxorubicin-stimulated phosphorylation of Bad in cells expressing dominant negative p38 MAPK was impeded by the inhibition of PI3-K. In addition to the impact on Bad phosphorylation, doxorubicin-treatment caused p38 MAPK-dependent downregulation of Bcl-xL protein.

Authors:
 [1];  [2];  [2];  [1]
  1. Lund University, Division of Experimental Pathology, Department of Laboratory Medicine, University Hospital MAS, Malmoe (Sweden)
  2. Laboratory of Cancer Genetics, Institute for Cancer Research and Treatment (IRCC), University of Turin, Candiolo (Tonga) (Italy)
Publication Date:
OSTI Identifier:
20854441
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 347; Journal Issue: 3; Other Information: DOI: 10.1016/j.bbrc.2006.06.159; PII: S0006-291X(06)01483-5; Copyright (c) 2006 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; APOPTOSIS; BORON CHLORIDES; DOXORUBICIN; IN VIVO; INHIBITION; PHOSPHORYLATION; PROTEINS

Citation Formats

Grethe, Simone, Coltella, Nadia, Di Renzo, Maria Flavia, and Poern-Ares, M Isabella. p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis. United States: N. p., 2006. Web. doi:10.1016/j.bbrc.2006.06.159.
Grethe, Simone, Coltella, Nadia, Di Renzo, Maria Flavia, & Poern-Ares, M Isabella. p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis. United States. https://doi.org/10.1016/j.bbrc.2006.06.159
Grethe, Simone, Coltella, Nadia, Di Renzo, Maria Flavia, and Poern-Ares, M Isabella. 2006. "p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis". United States. https://doi.org/10.1016/j.bbrc.2006.06.159.
@article{osti_20854441,
title = {p38 MAPK downregulates phosphorylation of Bad in doxorubicin-induced endothelial apoptosis},
author = {Grethe, Simone and Coltella, Nadia and Di Renzo, Maria Flavia and Poern-Ares, M Isabella},
abstractNote = {Doxorubicin is the anthracycline with the widest spectrum of antitumor activity, and it has been shown that the antitumor activity is mediated in vivo by selective triggering of apoptosis in proliferating endothelial cells. We studied cultured human endothelial cells and observed that doxorubicin-induced apoptosis was mediated by p38 mitogen-activated protein kinase (MAPK). Doxorubicin-provoked apoptosis was significantly inhibited by expression of dominant negative p38 MAPK or pharmacological inhibition with SB203580. Furthermore, blocking phosphatidylinositol-3-kinase/Akt signaling significantly increased doxorubicin-induced caspase-3 activity and cell death, indicating that Akt is a survival factor in this system. Notably, we also found that doxorubicin-provoked apoptosis included p38 MAPK-mediated inhibition of Akt and Bad phosphorylation. Furthermore, doxorubicin-stimulated phosphorylation of Bad in cells expressing dominant negative p38 MAPK was impeded by the inhibition of PI3-K. In addition to the impact on Bad phosphorylation, doxorubicin-treatment caused p38 MAPK-dependent downregulation of Bcl-xL protein.},
doi = {10.1016/j.bbrc.2006.06.159},
url = {https://www.osti.gov/biblio/20854441}, journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 3,
volume = 347,
place = {United States},
year = {Fri Sep 01 00:00:00 EDT 2006},
month = {Fri Sep 01 00:00:00 EDT 2006}
}