PMID- 23141142
OWN - NLM
STAT- MEDLINE
DCOM- 20130619
LR  - 20161125
IS  - 1096-0023 (Electronic)
IS  - 1043-4666 (Linking)
VI  - 61
IP  - 1
DP  - 2013 Jan
TI  - Tumour necrosis factor alpha down-regulates the expression of peroxisome 
      proliferator activated receptor alpha (PPARalpha) in human hepatocarcinoma HepG2 
      cells by activation of NF-kappaB pathway.
PG  - 266-74
LID - S1043-4666(12)00740-5 [pii]
LID - 10.1016/j.cyto.2012.10.007 [doi]
AB  - Peroxisome proliferator activated receptor-alpha (PPARalpha) plays a major role in 
      the regulation of lipid and glucose homeostasis, and inflammatory responses. The 
      objectives of the study were to systematically investigate the effects of TNF-alpha 
      and its regulatory pathway on PPARalpha expression in HepG2 cells using Real-Time 
      RT-PCR and western blot analysis. Here, TNF-alpha suppressed PPARalpha mRNA expression in 
      a dose- and time-dependent manner at the level of gene transcription. 
      Pre-treatment of cells with 10muM of Wedelolactone for 2h was sufficient to 
      restore PPARalpha expression to basal levels and also affected the expression of 
      PPARalpha-regulated genes. This study also demonstrated that TNF-alpha represses PPARalpha 
      expression by augmenting the activity of canonical NF-kappaB signalling pathway. This 
      was shown by the abrogation of TNF-alpha-mediated PPARalpha down-regulation, after both 
      p65 and p50 were knocked down via siRNA. The IKK contributes to IkappaBalpha degradation 
      and mediates inducible phosphorylation of p105 at Ser933. Surprisingly, 
      phosphorylation of p65 at Ser468 and Ser536 were severely abrogated with 
      Wedelolactone inhibition, suggesting that Ser468 and Ser536, but not Ser276, may 
      mediate the TNF-alpha inhibitory action on PPARalpha gene expression. These results 
      suggest that TNF-alpha might, at least in part, suppress PPARalpha expression through 
      activation of IKK/p50/p105/p65 pathway. Furthermore, phosphorylation of p65 at 
      Ser468 and Ser536 may play a crucial role in the mechanism that limits PPARalpha 
      production in the human HepG2 cells.
CI  - Copyright (c) 2012 Elsevier Ltd. All rights reserved.
FAU - Lim, Wyi Sian
AU  - Lim WS
AD  - Department of Biomedical Science, Faculty of Science, Universiti Tunku Abdul 
      Rahman, Bandar Barat, 31900 Kampar, Perak, Malaysia.
FAU - Ng, Di Lin
AU  - Ng DL
FAU - Kor, Sue Bee
AU  - Kor SB
FAU - Wong, Hong Kin
AU  - Wong HK
FAU - Tengku-Muhammad, Tengku Sifzizul
AU  - Tengku-Muhammad TS
FAU - Choo, Quok Cheong
AU  - Choo QC
FAU - Chew, Choy Hoong
AU  - Chew CH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121108
PL  - England
TA  - Cytokine
JT  - Cytokine
JID - 9005353
RN  - 0 (Coumarins)
RN  - 0 (NF-kappa B)
RN  - 0 (NF-kappa B p50 Subunit)
RN  - 0 (NFKB1 protein, human)
RN  - 0 (PPAR alpha)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Transcription Factor RelA)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0K6L725GNS (wedelolactone)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
EIN - Cytokine. 2013 Feb;61(2):691
MH  - Carcinoma, Hepatocellular/*metabolism
MH  - Cell Line, Tumor
MH  - Coumarins/pharmacology
MH  - Down-Regulation
MH  - Hep G2 Cells
MH  - Humans
MH  - I-kappa B Kinase/genetics/metabolism
MH  - Liver Neoplasms/metabolism
MH  - NF-kappa B/*metabolism
MH  - NF-kappa B p50 Subunit/genetics/metabolism
MH  - PPAR alpha/*biosynthesis/genetics
MH  - Phosphorylation
MH  - RNA Interference
MH  - RNA, Messenger/biosynthesis
MH  - RNA, Small Interfering
MH  - Signal Transduction/genetics
MH  - Transcription Factor RelA/genetics
MH  - Tumor Necrosis Factor-alpha/*metabolism
EDAT- 2012/11/13 06:00
MHDA- 2013/06/20 06:00
CRDT- 2012/11/13 06:00
PHST- 2012/04/23 00:00 [received]
PHST- 2012/09/27 00:00 [revised]
PHST- 2012/10/10 00:00 [accepted]
PHST- 2012/11/13 06:00 [entrez]
PHST- 2012/11/13 06:00 [pubmed]
PHST- 2013/06/20 06:00 [medline]
AID - S1043-4666(12)00740-5 [pii]
AID - 10.1016/j.cyto.2012.10.007 [doi]
PST - ppublish
SO  - Cytokine. 2013 Jan;61(1):266-74. doi: 10.1016/j.cyto.2012.10.007. Epub 2012 Nov 
      8.