Down-regulation of Fas-mediated apoptosis by plasma transglutaminase factor XIII that catalyzes fetal-specific cross-link of the Fas molecule.
The Fas antigen, also designated as APO-1 or CD95, is a member of the tumor necrosis factor receptor superfamily and can mediate apoptotic cell death in various cells. We report here that blood coagulation factor XIII (plasma transglutaminase, fibrin stabilizing factor) inhibits apoptosis induced by a cytotoxic anti-Fas monoclonal antibody in Jurkat cells. When cells were treated with the antibody in fetal calf serum-containing media, higher-molecular-weight (180K) polypeptides containing Fas molecule were detected by immunoblotting. Under conditions where the transglutaminase activity was eliminated or suppressed, the cross-link of Fas was not observed, and concurrently cell death was hastened. Moreover, an antibody against factor XIII strongly accelerated the Fas-mediated apoptosis. Furthermore, addition of partially purified factor XIII neutralized the apoptosis-promoting effect of anti-factor XIII antibody, indicating that this enzyme is involved in cross-link of Fas and down-regulates Fas-mediated apoptotic cell death. Significantly, the cross-link of Fas was seen only in fetal calf serum but not in newly-born calf serum, 1-year-old calf serum or adult bovine serum. These data suggest that plasma transglutaminase factor XIII may play a key role in fetal development of vertebrates via cross-link of Fas antigen.
Laboratory Center for Proteomics Research, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Section of Biochemistry and Molecular Biology, Department of Medical Sciences, Miyazaki Medical College, University of Miyazaki, Kihara, Kiyotake, Miyazaki 889-1692, Japan.
Hidehiko
H
Kikuchi
Laboratory Center for Proteomics Research, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; Department of Biochemistry, Kawasaki Medical School, Matsushima, Kurashiki, Okayama 701-0192, Japan.
Futoshi
F
Kuribayashi
Laboratory Center for Proteomics Research, The Institute of Medical Science, The University of Tokyo, Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Electronic address: ohmi@ims.u-tokyo.ac.jp.
Shinobu
S
Imajoh-Ohmi
D000911:Antibodies, Monoclonal / Q000378:metabolism; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis; D002384:Catalysis; D015536:Down-Regulation; D026122:Factor XIIIa / Q000378:metabolism*; D047109:Fetal Development; D005333:Fetus / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D019014:fas Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; C411023:anti-Fas monoclonal antibody; D019014:fas Receptor; D026122:Factor XIIIa
1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid acetoxymethyl ester; Apoptosis; BAPTA-AM; Cross-link; FCS; Factor XIII; Fas antigen; Fas ligand; FasL; Fetal development; KLH; MDC; SAF; TCA; TNF; TNF-related apoptosis-inducing ligand; TRAIL; Transglutaminase; fetal calf serum; keyhole lympet hemocyanin; mAb; monoclonal antibody; monodansylcadaverine; serum anti-apoptosis factor; trichloroacetic acid; tumor necrosis factor