Anti-apoptotic peptides protect against radiation-induced cell death.
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 15Gy radiation. In mice exposed to 5Gy 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.
McConnell
Kevin W
KW
Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
Muenzer
Jared T
JT
Chang
Kathy C
KC
Davis
Chris G
CG
McDunn
Jonathan E
JE
Coopersmith
Craig M
CM
Hilliard
Carolyn A
CA
Hotchkiss
Richard S
RS
Grigsby
Perry W
PW
Hunt
Clayton R
CR
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D002460:Cell Line; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010455:Peptides / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects*
D010455:Peptides; D011837:Radiation-Protective Agents