A role of fas-associated death domain (FADD) in increased apoptosis in aged humans.
Fas-associated death domain (FADD) is an adapter protein that is recruited to the death-inducing signaling complex (DISC) during signaling via death receptors. FADD is a common conduit in both CD95-mediated and TNF-R-mediated apoptosis. In aging, T cells show increased susceptibility to death receptor-induced apoptosis. Therefore, in this investigation, we have examined the role of FADD in increased TNF-alpha-induced apoptosis of lymphocytes from aged humans. Our study shows that FADD expression is increased in lymphocytes from aged humans as compared to those from young subjects. Furthermore, transfection of aged lymphocytes with FADD dominant negative (FADD dn) plasmid resulted in the reduction of TNF-induced apoptosis in aged lymphocytes to a level comparable to that of young subjects. In addition, overexpression of FADD by transfection of lymphocytes from young subjects with wild-type FADD (FADD wt) resulted in increased apoptosis of young lymphocytes to a level comparable to that of young subjects. These data suggest that FADD plays an important role in increased apoptosis in aged lymphocytes signaled via TNF-R.
Molecular Biology and Cellular Immunology Laboratories, Division of Basic and Clinical Immunology, University of California, Irvine, Irvine, California 92697, USA. sgupta@uci.edu
Sudhir
S
Gupta
Choong
C
Kim
Leman
L
Yel
Sastry
S
Gollapudi
D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000276:immunology / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D019014:fas Receptor / Q000276:immunology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D019014:fas Receptor