Anti-apoptotic peptides protect against radiation-induced cell death

Kevin W. McConnell, Jared T. Muenzer, Kathy C. Chang, Chris G. Davis, Jonathan E. McDunn, Craig M. Coopersmith, Carolyn A. Hilliard, Richard S. Hotchkiss, Perry W. Grigsby, Clayton R. Hunt

Research output: Contribution to journalArticle

24 Scopus citations

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.

Original languageEnglish
Pages (from-to)501-507
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume355
Issue number2
DOIs
StatePublished - Apr 6 2007

Keywords

  • Apoptosis
  • BH4
  • Bcl-xL
  • Lymphocyte
  • Radioprotectants
  • TAT

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    McConnell, K. W., Muenzer, J. T., Chang, K. C., Davis, C. G., McDunn, J. E., Coopersmith, C. M., Hilliard, C. A., Hotchkiss, R. S., Grigsby, P. W., & Hunt, C. R. (2007). Anti-apoptotic peptides protect against radiation-induced cell death. Biochemical and Biophysical Research Communications, 355(2), 501-507. https://doi.org/10.1016/j.bbrc.2007.01.180