TNF receptor deficiency reveals a translational control mechanism for adriamycin-induced Fas expression in cardiac tissues.
Adriamycin, ADR, a potent chemotherapeutic agent, has been demonstrated to cause cardiomyocyte apoptosis, in part, via the Fas/Fas ligand-mediated cell death pathway. Our previous studies suggested that TNF-alpha receptors may mediate cardioprotection against ADR toxicity by the suppression of the Fas-mediated pathway. However, the role of TNF-alpha receptors in this process is unclear. In the present study, we extended our initial observation to determine the molecular mechanisms by which ADR induced Fas expression in the presence and absence of TNF receptors. Our results demonstrated that ADR-mediated p53 and AP-1 interaction and increased Fas mRNA levels independent of TNF receptors. However, the levels of Fas proteins only increased in the cardiac tissues of TNF receptor-deficient mice. These results demonstrated that the suppression of ADR-induced Fas expression by TNF receptors was not regulated at transcriptional levels, but may be regulated at a translational level.
Lien
Yu-Chin
YC
Graduate Center for Toxicology, University of Kentucky, Lexington, KY 40536, USA.
Daosukho
Chotiros
C
St Clair
Daret K
DK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D004317:Doxorubicin / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014176:Protein Biosynthesis; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism*
D000903:Antibiotics, Antineoplastic; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D018808:Transcription Factor AP-1; D016159:Tumor Suppressor Protein p53; D019014:fas Receptor; D004317:Doxorubicin