Unknown

Dataset Information

0

The cytoprotective effects of tumor necrosis factor are conveyed through tumor necrosis factor receptor-associated factor 2 in the heart.


ABSTRACT: Activation of both type 1 and type 2 tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) confers cytoprotection in cardiac myocytes. Noting that the scaffolding protein TNF receptor-associated factor 2 (TRAF2) is common to both TNF receptors, we hypothesized that the cytoprotective responses of TNF were mediated through TRAF2.Mice with cardiac-restricted overexpression of low levels of TNF (MHCsTNF(3)) and TRAF2 (MHC-TRAF2(LC)) and mice lacking TNFR1, TNFR2, and TNFR1/TNFR2 were subjected to ischemia (30 minutes) reperfusion (30 minutes) injury ex vivo using a Langendorff apparatus. MHCsTNF(3) mice were protected against ischemia-reperfusion injury as shown by a significant approximately 30% greater left ventricular developed pressure, approximately 80% lower creatine kinase release, and Evans blue dye uptake compared with littermates. The extent of ischemia-reperfusion induced injury was similar in wild-type, TNFR1, and TNFR2 deficient mice; however, mice lacking TNFR1/TNFR2 had a significant approximately 40% lower left ventricular developed pressure, a approximately 65% greater creatine kinase release, and approximately 40% greater Evans blue dye uptake compared with littermates. Interestingly, MHC-TRAF2(LC) mice had a significant approximately 50% lower left ventricular developed pressure, a approximately 70% lower creatine kinase release, and approximately 80% lower Evans blue dye uptake compared with littermate controls after ischemia-reperfusion injury. Biochemical analysis of the MHC-TRAF2(LC) hearts showed that there was activation of nuclear factor-kappaB but not c-Jun N-terminal kinase activation.Taken together, these results suggest that TNF confers cytoprotection in the heart through TRAF2-mediated activation of nuclear factor-kappaB.

SUBMITTER: Burchfield JS 

PROVIDER: S-EPMC2910515 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

altmetric image

Publications

The cytoprotective effects of tumor necrosis factor are conveyed through tumor necrosis factor receptor-associated factor 2 in the heart.

Burchfield Jana S JS   Dong Jian-Wen JW   Sakata Yasushi Y   Gao Feng F   Tzeng Huei-Ping HP   Topkara Veli K VK   Entman Mark L ML   Sivasubramanian Natarajan N   Mann Douglas L DL  

Circulation. Heart failure 20091030 1


<h4>Background</h4>Activation of both type 1 and type 2 tumor necrosis factor (TNF) receptors (TNFR1 and TNFR2) confers cytoprotection in cardiac myocytes. Noting that the scaffolding protein TNF receptor-associated factor 2 (TRAF2) is common to both TNF receptors, we hypothesized that the cytoprotective responses of TNF were mediated through TRAF2.<h4>Methods and results</h4>Mice with cardiac-restricted overexpression of low levels of TNF (MHCsTNF(3)) and TRAF2 (MHC-TRAF2(LC)) and mice lacking  ...[more]

Similar Datasets

| S-EPMC3672470 | biostudies-literature
| S-EPMC3084962 | biostudies-literature
| S-EPMC6549921 | biostudies-literature
| S-EPMC4571974 | biostudies-literature
| S-EPMC5529482 | biostudies-literature
| S-EPMC9170173 | biostudies-literature
| S-EPMC7714153 | biostudies-literature
| S-EPMC4030310 | biostudies-literature
| S-EPMC4836215 | biostudies-literature
| S-EPMC5898986 | biostudies-literature