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Title: Anti-apoptotic peptides protect against radiation-induced cell death

Abstract

The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues.

Authors:
 [1];  [2];  [3];  [3];  [3];  [1];  [4];  [5];  [1];  [4];  [5];  [6]
  1. Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110 (United States)
  2. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO 63110 (United States)
  3. Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 (United States)
  4. (United States)
  5. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110 (United States)
  6. Department of Radiation Oncology, Washington University School of Medicine, St. Louis, MO 63110 (United States). E-mail: chunt@radonc.wustl.edu
Publication Date:
OSTI Identifier:
20979872
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 355; Journal Issue: 2; Other Information: DOI: 10.1016/j.bbrc.2007.01.180; PII: S0006-291X(07)00263-X; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRONMENTAL POLLUTANT EFFECTS ON LIVING ORGANISMS AND BIOLOGICAL MATERIALS; APOPTOSIS; HAZARDS; IN VITRO; IN VIVO; IRRADIATION; LYMPHOCYTES; MICE; PEPTIDES; RADIATION PROTECTION; THYMOCYTES

Citation Formats

McConnell, Kevin W., Muenzer, Jared T., Chang, Kathy C., Davis, Chris G., McDunn, Jonathan E., Coopersmith, Craig M., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Hilliard, Carolyn A., Hotchkiss, Richard S., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Grigsby, Perry W., and Hunt, Clayton R. Anti-apoptotic peptides protect against radiation-induced cell death. United States: N. p., 2007. Web. doi:10.1016/j.bbrc.2007.01.180.
McConnell, Kevin W., Muenzer, Jared T., Chang, Kathy C., Davis, Chris G., McDunn, Jonathan E., Coopersmith, Craig M., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Hilliard, Carolyn A., Hotchkiss, Richard S., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Grigsby, Perry W., & Hunt, Clayton R. Anti-apoptotic peptides protect against radiation-induced cell death. United States. doi:10.1016/j.bbrc.2007.01.180.
McConnell, Kevin W., Muenzer, Jared T., Chang, Kathy C., Davis, Chris G., McDunn, Jonathan E., Coopersmith, Craig M., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Hilliard, Carolyn A., Hotchkiss, Richard S., Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, Grigsby, Perry W., and Hunt, Clayton R. Fri . "Anti-apoptotic peptides protect against radiation-induced cell death". United States. doi:10.1016/j.bbrc.2007.01.180.
@article{osti_20979872,
title = {Anti-apoptotic peptides protect against radiation-induced cell death},
author = {McConnell, Kevin W. and Muenzer, Jared T. and Chang, Kathy C. and Davis, Chris G. and McDunn, Jonathan E. and Coopersmith, Craig M. and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 and Hilliard, Carolyn A. and Hotchkiss, Richard S. and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110 and Grigsby, Perry W. and Hunt, Clayton R.},
abstractNote = {The risk of terrorist attacks utilizing either nuclear or radiological weapons has raised concerns about the current lack of effective radioprotectants. Here it is demonstrated that the BH4 peptide domain of the anti-apoptotic protein Bcl-xL can be delivered to cells by covalent attachment to the TAT peptide transduction domain (TAT-BH4) and provide protection in vitro and in vivo from radiation-induced apoptotic cell death. Isolated human lymphocytes treated with TAT-BH4 were protected against apoptosis following exposure to 15 Gy radiation. In mice exposed to 5 Gy radiation, TAT-BH4 treatment protected splenocytes and thymocytes from radiation-induced apoptotic cell death. Most importantly, in vivo radiation protection was observed in mice whether TAT-BH4 treatment was given prior to or after irradiation. Thus, by targeting steps within the apoptosis signaling pathway it is possible to develop post-exposure treatments to protect radio-sensitive tissues.},
doi = {10.1016/j.bbrc.2007.01.180},
journal = {Biochemical and Biophysical Research Communications},
number = 2,
volume = 355,
place = {United States},
year = {Fri Apr 06 00:00:00 EDT 2007},
month = {Fri Apr 06 00:00:00 EDT 2007}
}