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Title: Desferrioxamine (DFX) induces apoptosis through the p38-caspase8-Bid-Bax pathway in PHA-stimulated human lymphocytes

Abstract

Desferrioxamine (DFX) induces apoptosis in human lymphocytes, although the mechanism leading to cell death is unclear. Therefore, we investigated the signaling pathways implicated in DFX-induced apoptosis in lymphocytes. DFX treatment activated caspase-9, caspase-3, and caspase-8. DFX-induced apoptosis was inhibited by both z-IETD-fmk and z-DEVD-fmk. DFX treatment also enhanced caspase-8 activity, Bid cleavage, and the conformational activation of Bax. DFX treatment activated two MAPKs, p38 and JNK, and induced the phosphorylation of two proteins in the p38 pathway, MKK3 and MKK6. DFX treatment also increased the phosphorylation of two downstream targets of p38, ATF-2 and MAPKAPK2, indicating that DFX promotes p38 activity. In addition, the selective p38 inhibitor SB203580 suppressed DFX-induced apoptosis and caspase-8 activation, whereas the JNK inhibitor, SP600125, and the ERK inhibitor, PD98059, had no effect. Our results suggest that DFX-induced apoptosis is mediated by the p38 pathway and a caspase-8-dependent Bid-Bax pathway in human lymphocytes.

Authors:
 [1];  [1]
  1. School of Public Health, Seoul National University, 28 Yunkeun-dong, Chongno-ku, Seoul 110-460 (Korea, Republic of)
Publication Date:
OSTI Identifier:
21140797
Resource Type:
Journal Article
Journal Name:
Toxicology and Applied Pharmacology
Additional Journal Information:
Journal Volume: 228; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.11.022; PII: S0041-008X(07)00537-6; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTIOXIDANTS; APOPTOSIS; CLEAVAGE; LYMPHOCYTES; PHOSPHORYLATION; PHOSPHOTRANSFERASES; PROPOSALS

Citation Formats

Kim, Byeong-Mo, Cancer Research Institute, Seoul National University, Seoul 110-799, and Chung, Hai-Won. Desferrioxamine (DFX) induces apoptosis through the p38-caspase8-Bid-Bax pathway in PHA-stimulated human lymphocytes. United States: N. p., 2008. Web. doi:10.1016/j.taap.2007.11.022.
Kim, Byeong-Mo, Cancer Research Institute, Seoul National University, Seoul 110-799, & Chung, Hai-Won. Desferrioxamine (DFX) induces apoptosis through the p38-caspase8-Bid-Bax pathway in PHA-stimulated human lymphocytes. United States. https://doi.org/10.1016/j.taap.2007.11.022
Kim, Byeong-Mo, Cancer Research Institute, Seoul National University, Seoul 110-799, and Chung, Hai-Won. 2008. "Desferrioxamine (DFX) induces apoptosis through the p38-caspase8-Bid-Bax pathway in PHA-stimulated human lymphocytes". United States. https://doi.org/10.1016/j.taap.2007.11.022.
@article{osti_21140797,
title = {Desferrioxamine (DFX) induces apoptosis through the p38-caspase8-Bid-Bax pathway in PHA-stimulated human lymphocytes},
author = {Kim, Byeong-Mo and Cancer Research Institute, Seoul National University, Seoul 110-799 and Chung, Hai-Won},
abstractNote = {Desferrioxamine (DFX) induces apoptosis in human lymphocytes, although the mechanism leading to cell death is unclear. Therefore, we investigated the signaling pathways implicated in DFX-induced apoptosis in lymphocytes. DFX treatment activated caspase-9, caspase-3, and caspase-8. DFX-induced apoptosis was inhibited by both z-IETD-fmk and z-DEVD-fmk. DFX treatment also enhanced caspase-8 activity, Bid cleavage, and the conformational activation of Bax. DFX treatment activated two MAPKs, p38 and JNK, and induced the phosphorylation of two proteins in the p38 pathway, MKK3 and MKK6. DFX treatment also increased the phosphorylation of two downstream targets of p38, ATF-2 and MAPKAPK2, indicating that DFX promotes p38 activity. In addition, the selective p38 inhibitor SB203580 suppressed DFX-induced apoptosis and caspase-8 activation, whereas the JNK inhibitor, SP600125, and the ERK inhibitor, PD98059, had no effect. Our results suggest that DFX-induced apoptosis is mediated by the p38 pathway and a caspase-8-dependent Bid-Bax pathway in human lymphocytes.},
doi = {10.1016/j.taap.2007.11.022},
url = {https://www.osti.gov/biblio/21140797}, journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 228,
place = {United States},
year = {Tue Apr 01 00:00:00 EDT 2008},
month = {Tue Apr 01 00:00:00 EDT 2008}
}