Tumor Necrosis Factor Alpha-induced Apoptosis in Cardiac Myocytes: Involvement of the Sphingolipid Signaling Cascade in Cardiac Cell Death.
Krown, Kevin A.; Page, M. Trevor; Nguyen, Cuong; Zechner, Dietmar; Gutierrez, Veronica; Comstock, Kevyn L.; Glembotski, Christopher C.; Quintana, Penelope J.E.; Sabbadini, Roger A.
[Article] Journal of Clinical Investigation. 98(12):2854-2865, December 15, 1996.

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In the present study, it was shown that physiologically relevant levels of the proinflammatory cytokine TNF alpha induced apoptosis in rat cardiomyocytes in vitro, as quantified by single cell microgel electrophoresis of nuclei ("cardiac comets") as well as by morphological and biochemical criteria. It was also shown that TNF alpha stimulated production of the endogenous second messenger, sphingosine, suggesting sphingolipid involvement in TNF alpha-mediated cardiomyocyte apoptosis. Consistent with this hypothesis, sphingosine strongly induced cardiomyocyte apoptosis. The ability of the appropriate stimulus to drive cardiomyocytes into apoptosis indicated that these cells were primed for apoptosis and were susceptible to clinically relevant apoptotic triggers, such as TNF alpha. These findings suggest that the elevated TNF alpha levels seen in a variety of clinical conditions, including sepsis and ischemic myocardial disorders, may contribute to TNF alpha-induced cardiac cell death. Cardiomyocyte apoptosis is also discussed in terms of its potential beneficial role in limiting the area of cardiac cell involvement as a consequence of myocardial infarction, viral infection, and primary cardiac tumors. (J. Clin. Invest. 1996. 98:2854-2865)

Copyright (C) 1996 The American Society for Clinical Investigation, Inc.