BH4-domain peptide from Bcl-xL exerts anti-apoptotic activity in vivo.

Abstract

The Bcl-2 family of proteins regulates apoptosis chiefly by controlling mitochondrial membrane permeability. It has previously been shown that the BH4 domain of Bcl-2/Bcl-xL is essential for the prevention of apoptotic mitochondrial changes, including the release of cytochrome c and apoptotic cell death. We have previously reported that BH4 peptide fused to the protein transduction domain of HIV-1 TAT protein (TAT-BH4) significantly inhibits etoposide-induced apoptosis in a cell line. This time, we investigated whether TAT-BH4 peptide was cytoprotective in ex vivo and in vivo rodent models. Intraperitoneal injection of TAT-BH4 peptide greatly inhibited X-ray-induced apoptosis in the small intestine of mice and partially suppressed Fas-induced fulminant hepatitis. In addition, this peptide markedly suppressed heart failure after ischemia-reperfusion injury in isolated rat heart, probably by preventing mitochondrial dysfunction. These findings demonstrate that TAT-BH4 peptide exerts anti-apoptotic activity both in vivo and ex vivo, and imply that it may be a useful therapeutic agent for diseases involving mitochondrial dysfunction and apoptosis.

• Authors: Rie Sugioka, Shigeomi Shimizu, Toshihiro Funatsu, Hiroshi Tamagawa, Yoshiki Sawa, Toru Kawakami, Yoshihide Tsujimoto
• Journal: Oncogene (Oncogene) Vol. 22 Issue 52 Pg. 8432-40 (Nov 20 2003) ISSN: 0950-9232 [Print] England
• PMID: 14627984 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• BCL2L1 protein, human
• Bcl2l1 protein, mouse
• Peptides
• Proto-Oncogene Proteins c-bcl-2
• bcl-X Protein

Topics

• Animals
• Apoptosis (drug effects, radiation effects)
• HeLa Cells
• Hepatitis (drug therapy)
• Humans
• Intestine, Small (drug effects, radiation effects)
• Mice
• Myocardial Reperfusion Injury (drug therapy)
• Peptides (metabolism, pharmacology)
• Protein Structure, Tertiary
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• X-Rays
• bcl-X Protein