You are here
Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues.
Title | Cellular FLIP is expressed in cardiomyocytes and down-regulated in TUNEL-positive grafted cardiac tissues. |
Publication Type | Journal Article |
Year of Publication | 2000 |
Authors | Imanishi, T, Murry, CE, Reinecke, H, Hano, T, Nishio, I, Liles, WC, Hofsta, L, Kim, K, O'Brien, KD, Schwartz, SM, Han, DK |
Journal | Cardiovasc Res |
Volume | 48 |
Issue | 1 |
Pagination | 101-10 |
Date Published | 2000 Oct |
ISSN | 0008-6363 |
Keywords | Adult, Animals, Animals, Newborn, Antigens, CD95, Apoptosis, Blotting, Western, Caspases, Cell Transplantation, Coculture Techniques, DNA Fragmentation, Dogs, Enzyme Inhibitors, Fas Ligand Protein, Female, Gene Expression, Heart Failure, Humans, Immunohistochemistry, In Situ Hybridization, In Situ Nick-End Labeling, Leukocytes, Mononuclear, Lymphocyte Activation, Male, Membrane Glycoproteins, Middle Aged, Models, Animal, Myocardium, Rats, Rats, Inbred F344, RNA, Messenger |
Abstract | OBJECTIVE: c-FLIP is a natural homologue of caspase 8, and may antagonize activation of death pathways mediated by FADD. c-FLIP is highly expressed in the heart, and a recent report suggests that c-FLIP may protect against certain types of myocyte death. The present study was designed to define the expression patterns of c-FLIP in the heart. METHODS: The expression pattern of c-FLIP in end-stage human hearts, and rat cardiomyocyte grafting models was analyzed by in situ hybridization, immunohistochemistry and TUNEL assay. In addition, to determine whether Fas-dependent pathway is active in cardiomyocytes in vitro, we examined whether activated monocytes can kill neonatal cardiomyocytes in a co-culture system. RESULTS: c-FLIP mRNA and protein were abundantly expressed in normal cardiomyocytes from failing human heart. In animal models, c-FLIP protein was absent in TUNEL-positive grafted cardiomyocytes. Double staining demonstrated that c-FLIP-positive cells rarely had fragmented DNA, while TUNEL-positive cells rarely contained c-FLIP. Finally, activated monocytes induced death of neonatal rat cardiomyocytes via the Fas/FasL system. CONCLUSIONS: Loss of c-FLIP expression correlates with cardiomyocyte cell death. We hypothesize that diminished c-FLIP expression may predispose cardiomyocytes to apoptotic death. |
Alternate Journal | Cardiovasc. Res. |
PubMed ID | 11033112 |