Please use this identifier to cite or link to this item:
|Title:||Fas-associated death-domain protein inhibits TNF-? mediated NF-?B activation in cardiomyocytes||Authors:||Chao W.
Tumor necrosis factor
|Issue Date:||2005||Publisher:||APS||Citation:||Chao W., Shen Y., Li L., Zhao H., Meiler S.E., Cook S.A., Rosenzweig A. (2005). Fas-associated death-domain protein inhibits TNF-? mediated NF-?B activation in cardiomyocytes. American Journal of Physiology - Heart and Circulatory Physiology 289 (5 58-5) : H2073-H2080. ScholarBank@NUS Repository. https://doi.org/10.1152/ajpheart.01216.2004||Abstract:||Fas-associated death-domain protein (FADD) is an adaptor molecule that links death receptors to caspase-8 in many cell types including cardiomyocytes (CMs). Although FADD has previously been reported to play an important role in CM apoptosis, the effect of FADD on CM TNF-? signaling, which is a proinflammatory pathway, has not been delineated. To investigate the role of FADD in CM NF-kB activation, we utilized adenoviral gene transfer of wild-type FADD and a truncation mutant that lacks the death-effector domain (FADD-DED) in rat CMs in vitro. TNF-? activated NF-kB in CMs as demonstrated by phosphorylation and degradation of inhibitory-kB (IkB)-?-enhanced nuclear p65 and NF-kB DNA-binding activity as well as increased mRNA for the NF-kB-dependent adhesion molecule VCAM-1 (19 � 4.1-fold) as measured by quantitative RT-PCR. Gene transfer of FADD inhibited TNF-?-induced IkB-? phosphorylation, decreased p65 nuclear translocation and NF-kB DNA-binding activity, and reduced VCAM-1 transcript levels by 53-65%. Interestingly, FADD-DED exhibited a similar but weaker inhibitory effect on NF-kB activation. The effects of FADD on NF-kB were cell-type specific. FADD expression also inhibited TNF-?-mediated NF-kB activation in human endothelial cells but not in rat pulmonary artery smooth muscle cells. In contrast, FADD expression actually activated NF-kB in human embryonic kidney (HEK)-293 cells. In CMs, FADD inhibited NF-kB activation as well as phosphorylation of IkB-? and IkB kinase (IKK)-? in response to cytokine stimulation or expression of the upstream kinases NF-kB-inducing kinase and IKK-?. These data demonstrate that FADD inhibits NF-kB activation in CMs, and this inhibition likely occurs at the level of phosphorylation and activation of IKK-?. Copyright � 2005 the American Physiological Society.||Source Title:||American Journal of Physiology - Heart and Circulatory Physiology||URI:||http://scholarbank.nus.edu.sg/handle/10635/149282||ISSN:||3636135||DOI:||10.1152/ajpheart.01216.2004|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Oct 18, 2020
WEB OF SCIENCETM
checked on Dec 26, 2018
checked on Oct 16, 2020
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.