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- W1994419384 abstract "Previous studies in isolated cardiac myocytes have shown that tumor necrosis factor (TNF)-alpha provokes increased expression of 27- and 70-kD stress proteins as well as manganese superoxide dismutase, suggesting that TNF-alpha might play a role in mediating stress responses in the heart.To determine whether TNF-alpha stimulation would protect isolated cardiac myocytes against environmental stress, myocyte cultures were pretreated with TNF-alpha for 12 hours and then subjected to continuous hypoxic injury (O2 content, 3 to 5 ppm) for 12 hours, followed by reoxygenation. Cell injury was assessed in terms of lactic dehydrogenase (LDH) release, 45Ca2+ uptake, and MTT metabolism. Pretreatment with TNF-alpha concentrations > or = 50 U/mL significantly attenuated LDH release by hypoxic cells compared with diluent-treated hypoxic cells. Similar findings were observed with respect to 45Ca2+ uptake and MTT metabolism in TNF-alpha-pretreated cells that were subjected to prolonged hypoxia. To determine the mechanism for the TNF-alpha-induced protective effect, the cells were pretreated with heat shock protein (HSP) 72 antisense oligonucleotides. These studies showed that the protective effect of TNF-alpha was not inhibited by antisense oligonucleotides, despite use of a concentration of antisense that was sufficient to attenuate the TNF-alpha-induced increase in HSP 72 expression. Subsequent studies using mutated TNF ligands showed that activation of both types 1 and 2 TNF receptors was sufficient to confer a protective response in isolated cardiac myocytes through an as yet unknown pathway(s).Taken together, the above observations demonstrate that TNF-alpha pretreatment confers resistance to hypoxic stress in the adult cardiac myocyte through a novel mechanism that appears to be different from but not necessarily exclusive of the protective response conferred by HSP 72 expression." @default.
- W1994419384 created "2016-06-24" @default.
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- W1994419384 date "1998-04-14" @default.
- W1994419384 modified "2023-09-26" @default.
- W1994419384 title "Tumor Necrosis Factor-α Confers Resistance to Hypoxic Injury in the Adult Mammalian Cardiac Myocyte" @default.
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- W1994419384 doi "https://doi.org/10.1161/01.cir.97.14.1392" @default.
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