Bax-inhibiting peptide derived from mouse and rat Ku70

Tomoyuki Yoshida; Ikuo Tomioka; Takako Nagahara; Trudy Holyst; Motoshi Sawada; Paulette Hayes; Vivian Gama; Misako Okuno; Yuhong Chen; Yasuyuki Abe; Tadashi Kanouchi; Hiroshi Sasada; Demin Wang; Takanori Yokota; Eimei Sato; Shigemi Matsuyama

doi:10.1016/j.bbrc.2004.07.054

Bax-inhibiting peptide derived from mouse and rat Ku70

Biochem Biophys Res Commun. 2004 Sep 3;321(4):961-6. doi: 10.1016/j.bbrc.2004.07.054.

Authors

Tomoyuki Yoshida¹, Ikuo Tomioka, Takako Nagahara, Trudy Holyst, Motoshi Sawada, Paulette Hayes, Vivian Gama, Misako Okuno, Yuhong Chen, Yasuyuki Abe, Tadashi Kanouchi, Hiroshi Sasada, Demin Wang, Takanori Yokota, Eimei Sato, Shigemi Matsuyama

Affiliation

¹ Blood Research Institute, The Blood Center of South Eastern Wisconsin and Department of Biochemistry, Medical College of Wisconsin, 8727 Watertown Plank Road, Milwaukee, WI 53226, USA.

PMID: 15358121
DOI: 10.1016/j.bbrc.2004.07.054

Abstract

Bax is a proapoptotic protein that plays a key role in the induction of apoptosis. Ku70 has activities to repair DNA damage in the nucleus and to suppress apoptosis by inhibiting Bax in the cytosol. We previously designed peptides based on the amino acid sequence of Bax-binding domain of human Ku70, and showed that these peptides bind Bax and inhibit cell death in human cell lines. In the present report, we examined the biological activities of other pentapeptides, VPTLK and VPALR, derived from mouse and rat Ku70. Cells in culture accumulated FITC-labeled VPTLK and VPALR, indicating that these peptides are cell permeable (human, mouse, rat, and porcine cells were examined). These peptides bound to Bax and suppressed cell death in various cell types including primary cultured cells. These data suggest that such Bax inhibiting peptides from three mammalian species may be used to protect healthy cells from apoptotic injury under pathological conditions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Animals
Antigens, Nuclear / chemistry
Antigens, Nuclear / genetics
Antigens, Nuclear / metabolism*
Apoptosis / drug effects
Cell Line
Cells, Cultured
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Etoposide / pharmacology
Female
Humans
Ku Autoantigen
Mice
Molecular Sequence Data
Oligopeptides / chemistry
Oligopeptides / metabolism
Oligopeptides / pharmacology*
Ovary / cytology
Ovary / drug effects
Ovary / metabolism
Proto-Oncogene Proteins / antagonists & inhibitors*
Proto-Oncogene Proteins / metabolism
Proto-Oncogene Proteins c-bcl-2*
Rats
Sequence Homology, Amino Acid
bcl-2-Associated X Protein

Substances

Antigens, Nuclear
BAX protein, human
Bax protein, mouse
Bax protein, rat
DNA-Binding Proteins
Oligopeptides
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-bcl-2
bcl-2-Associated X Protein
Etoposide
Xrcc6 protein, human
Xrcc6 protein, mouse
Xrcc6 protein, rat
Ku Autoantigen