TNF-α as a potential mediator of cardiac dysfunction due to intracellular Ca 2+-overload


Zhang M., Xu Y., Saini H. K. , TURAN B., Liu P. P. , Dhalla N. S.

Biochemical and Biophysical Research Communications, vol.327, no.1, pp.57-63, 2005 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 327 Issue: 1
  • Publication Date: 2005
  • Doi Number: 10.1016/j.bbrc.2004.11.131
  • Journal Name: Biochemical and Biophysical Research Communications
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.57-63
  • Keywords: pentoxifylline, Ca2+-paradox, tumor necrosis factor-alpha, nuclear factor-kappa B, cardiac dysfunction, NECROSIS-FACTOR-ALPHA, NF-KAPPA-B, OXIDATIVE STRESS, PROTEIN-KINASE, HEART-FAILURE, PENTOXIFYLLINE, ACTIVATION, EXPRESSION, MUSCLE, INFARCTION

Abstract

TNF-α has been shown to be involved in cardiac dysfunction during ischemia/reperfusion injury; however, no information regarding the status of TNF-α production in myocardial injury due to intracellular Ca 2+-overload is available in the literature. The intracellular Ca 2+-overload was induced in the isolated rat hearts subjected to 5 min Ca 2+-depletion and 30 min Ca 2+-repletion (Ca 2+-paradox). The Ca 2+-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-α content. The ratio of cytosolic to homogenate nuclear factor-κB (NFκB) was decreased whereas the ratio of phospho-NFκB to total NFκB was increased in the Ca 2+-paradox hearts. All these changes due to Ca 2+-paradox were significantly attenuated upon treating the hearts with 100 μM pentoxifylline. These results suggest that activation of NFκB and increased production of TNF-α may play an important role in cardiac injury due to intracellular Ca 2+-overload. © 2004 Elsevier Inc. All rights reserved.