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

Journal Article · Fri Sep 01 04:00:00 EDT 2006 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2006.06.159· OSTI ID:20854441

Grethe, Simone ^[1]; Coltella, Nadia ^[2]; Di Renzo, Maria Flavia ^[2]; Poern-Ares, M Isabella ^[1]

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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)

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.

• OSTI ID: 20854441
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 3 Vol. 347; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
BORON CHLORIDES
DOXORUBICIN
IN VIVO
INHIBITION
PHOSPHORYLATION
PROTEINS