title: Cell-permeable intrinsic cellular inhibitors of apoptosis protect and rescue intestinal epithelial cells from radiation-induced cell death.
abstract: One of the important mechanisms for gastrointestinal (GI) injury following high-dose radiation exposure is apoptosis of epithelial cells. X-linked inhibitor of apoptosis (XIAP) and cellular IAP2 (cIAP2) are intrinsic cellular inhibitors of apoptosis. In order to study the effects of exogenously added IAPs on apoptosis in intestinal epithelial cells, we constructed bacterial expression plasmids containing genes of XIAP (full-length, BIR2 domain and BIR3-RING domain with and without mutations of auto-ubiquitylation sites) and cIAP2 proteins fused to a protein-transduction domain (PTD) derived from HIV-1 Tat protein (TAT) and purified these cell-permeable recombinant proteins. When the TAT-conjugated IAPs were added to rat intestinal epithelial cells IEC6, these proteins were effectively delivered into the cells and inhibited apoptosis, even when added after irradiation. Our results suggest that PTD-mediated delivery of IAPs may have clinical potential, not only for radioprotection but also for rescuing the GI system from radiation injuries.
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan Department of Traumatology and Critical Care Medicine, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-city, Tokyo, 181-8611, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Matsuzaki-Horibuchi
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yasuda
authors.affiliation: Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan.
authors.forename: Nagako
authors.initials: N
authors.lastname: Sakaguchi
authors.affiliation: Department of Traumatology and Critical Care Medicine, Kyorin University Hospital, 6-20-2 Shinkawa, Mitaka-city, Tokyo, 181-8611, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamaguchi
authors.affiliation: National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba-city, Chiba 263-8555, Japan akashi@nirs.go.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Akashi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology* / Q000528:radiation effects*; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism* / Q000528:radiation effects; D051034:Inhibitor of Apoptosis Proteins / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000502:physiology; D051381:Rats; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000378:metabolism*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases