PMID- 22634003
OWN - NLM
STAT- MEDLINE
DCOM- 20120913
LR  - 20211021
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 423
IP  - 1
DP  - 2012 Jun 22
TI  - cAMP prevents TNF-induced apoptosis through inhibiting DISC complex formation in 
      rat hepatocytes.
PG  - 85-90
LID - 10.1016/j.bbrc.2012.05.087 [doi]
AB  - Tumor necrosis factor alpha (TNF) is a pleiotropic proinflammatory cytokine that 
      plays a role in immunity and the control of cell proliferation, cell 
      differentiation, and apoptosis. The pleiotropic nature of TNF is due to the 
      formation of different signaling complexes upon the binding of TNF to its 
      receptor, TNF receptor type 1 (TNFR1). TNF induces apoptosis in various mammalian 
      cells when the cells are co-treated with a transcription inhibitor like 
      actinomycin D (ActD). When TNFR1 is activated, it recruits an adaptor protein, 
      TNF receptor-associated protein with death domain (TRADD), through its 
      cytoplasmic death effector domain (DED). TRADD, in turn, recruits other signaling 
      proteins, including TNF receptor-associated protein 2 (TRAF2) and 
      receptor-associated protein kinase (RIPK) 1, to form a complex. Subsequently, 
      this complex combines with FADD and procaspase-8, converts into a death-inducing 
      signaling complex (DISC) to induce apoptosis. Cyclic AMP (cAMP) is a second 
      messenger that regulates various cellular processes such as cell proliferation, 
      gene expression, and apoptosis. cAMP analogues are reported to act as 
      anti-apoptotic agents in various cell types, including hepatocytes. We found that 
      a cAMP analogue, dibutyryl cAMP (db-cAMP), inhibits TNF+ActD-induced apoptosis in 
      rat hepatocytes. The protein kinase A (PKA) inhibitor KT-5720 reverses this 
      inhibitory effect of cAMP on apoptosis. Cytoprotection by cAMP involves 
      down-regulation of various apoptotic signal regulators like TRADD and FADD and 
      inhibition of caspase-8 and caspase-3 cleavage. We also found that cAMP exerts 
      its affect at the proximal level of TNF signaling by inhibiting the formation of 
      the DISC complex upon the binding of TNF to TNFR1. In conclusion, our study shows 
      that cAMP prevents TNF+ActD-induced apoptosis in rat hepatocytes by inhibiting 
      DISC complex formation.
CI  - Copyright (c) 2012 Elsevier Inc. All rights reserved.
FAU - Bhattacharjee, Rajesh
AU  - Bhattacharjee R
AD  - Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA 
      15213, USA.
FAU - Xiang, Wenpei
AU  - Xiang W
FAU - Wang, Yinna
AU  - Wang Y
FAU - Zhang, Xiaoying
AU  - Zhang X
FAU - Billiar, Timothy R
AU  - Billiar TR
LA  - eng
GR  - R37 GM044100/GM/NIGMS NIH HHS/United States
GR  - R37 GM44100/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120523
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Carbazoles)
RN  - 0 (Death Domain Receptor Signaling Adaptor Proteins)
RN  - 0 (Pyrroles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 58HV29I28S (KT 5720)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Apoptosis
MH  - Bucladesine/pharmacology
MH  - Carbazoles/pharmacology
MH  - Cells, Cultured
MH  - Cyclic AMP/*metabolism/pharmacology
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors
MH  - Death Domain Receptor Signaling Adaptor Proteins/*antagonists & 
      inhibitors/biosynthesis
MH  - Hepatocytes/drug effects/*metabolism
MH  - Pyrroles/pharmacology
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*metabolism/pharmacology
PMC - PMC3576132
MID - NIHMS380351
COIS- Conflict of Interest Authors do not have any financial relationship with the 
      granting authority. The authors declare that they have no conflict of interest.
EDAT- 2012/05/29 06:00
MHDA- 2012/09/14 06:00
PMCR- 2013/06/22
CRDT- 2012/05/29 06:00
PHST- 2012/05/09 00:00 [received]
PHST- 2012/05/16 00:00 [accepted]
PHST- 2012/05/29 06:00 [entrez]
PHST- 2012/05/29 06:00 [pubmed]
PHST- 2012/09/14 06:00 [medline]
PHST- 2013/06/22 00:00 [pmc-release]
AID - S0006-291X(12)00977-1 [pii]
AID - 10.1016/j.bbrc.2012.05.087 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2012 Jun 22;423(1):85-90. doi: 
      10.1016/j.bbrc.2012.05.087. Epub 2012 May 23.