title: TNF-alpha as a potential mediator of cardiac dysfunction due to intracellular Ca2+-overload.
abstract: TNF-alpha has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-alpha production in myocardial injury due to intracellular Ca2+-overload is available in the literature. The intracellular Ca2+-overload was induced in the isolated rat hearts subjected to 5 min Ca2+-depletion and 30 min Ca2+-repletion (Ca2+-paradox). The Ca2+-paradox hearts exhibited a dramatic depression in left ventricular developed pressure, a marked elevation in left ventricular end diastolic pressure, and more than a 4-fold increase in TNF-alpha content. The ratio of cytosolic to homogenate nuclear factor-kappaB (NFkappaB) was decreased whereas the ratio of phospho-NFkappaB to total NFkappaB was increased in the Ca2+-paradox hearts. All these changes due to Ca2+-paradox were significantly attenuated upon treating the hearts with 100 microM pentoxifylline. These results suggest that activation of NFkappaB and increased production of TNF-alpha may play an important role in cardiac injury due to intracellular Ca2+-overload.
authors.affiliation: Department of Physiology, St. Boniface General Hospital Research Center, Institute of Cardiovascular Sciences, Faculty of Medicine University of Manitoba, Winnipeg, Canada.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhang
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Xu
authors.forename: Harjot K
authors.initials: HK
authors.lastname: Saini
authors.forename: Belma
authors.initials: B
authors.lastname: Turan
authors.forename: Peter P
authors.initials: PP
authors.lastname: Liu
authors.forename: Naranjan S
authors.initials: NS
authors.lastname: Dhalla
mesh_terms: D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D002118:Calcium