Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression.

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dc.contributor.author Farrell, G
dc.contributor.author Larter, C
dc.contributor.author Hou, JY
dc.contributor.author Zhang, RH
dc.contributor.author Yeh, MM
dc.contributor.author Williams, J
dc.contributor.author Pena, A
dc.contributor.author Francisco, R
dc.contributor.author Osvath, SR
dc.contributor.author Brooling, J
dc.contributor.author Teoh, N
dc.contributor.author Sedger, LM
dc.date.accessioned 2011-02-07T06:24:06Z
dc.date.issued 2009-01
dc.identifier.citation Journal of Gastroenterology and Hepatology, 2009, 24 (3), pp. 443 - 452
dc.identifier.issn 0815-9319
dc.identifier.other C1UNSUBMIT en_US
dc.identifier.uri http://hdl.handle.net/10453/13712
dc.description.abstract Background and Aims: We examined extrinsic and intrinsic (endogenous) mitochondrial apoptosis pathways in experimental non-alcoholic steatohepatitis (NASH). Methods: To assess extrinsic pathways, we measured hepatic expression of death-inducing cytokine receptors (tumor necrosis factor-a-receptor (TNF-R)1, TNF-R2, Fas, and TNFa-related apoptosis-inducing ligand-receptor (TRAIL-R) mRNA, TUNEL, caspase 3 activation, liver injury and liver pathology in mice fed a methionine and choline deficient (MCD) diet. For endogenous stress pathways, we determined serum insulin-like growth factor-1 (IGF-1), hepatic p53, Bcl-XL, tBid and p21 expression. Results: Methionine and choline deficient feeding increased alanine aminotransferase (ALT) and apoptosis from day 10, without increases in TNF-R1, TNF-R2, and Fas. However, murine TRAIL receptors, particularly decoyTRAIL-R1/TNFRSFH23 and Killer/DR5 mRNA increased. MCD feeding enhanced hepatic p53 expression, corresponding to ~50% fall in serum IGF-1, decreased Bcl-XL, enhanced Bid cleavage to tBid, and up-regulation of p21. Nutritional restitution experiments showed that correcting either methionine or choline deficiency suppressed liver inflammation (extrinsic pathway), but failed to correct apoptosis, IGF-1 or p53. Conclusions: Methionine and choline deficiency lower IGF-1 to de-repress p53 during induction of steatohepatitis. The p53 induced by nutritional stress is biologically active in mediating mitochondrial cell death pathways, but may also be responsible for TRAIL receptor expression, thereby linking intrinsic and exogenous apoptosis pathways in NASH.
dc.publisher The Asia Pacific Association for Gastroenterology
dc.relation.isbasedon 10.1111/j.1440-1746.2009.05785.x
dc.title Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression.
dc.type Journal Article
dc.parent Journal of Gastroenterology and Hepatology
dc.journal.volume 3
dc.journal.volume 24
dc.journal.number 3 en_US
dc.publocation Asia en_US
dc.identifier.startpage 443 en_US
dc.identifier.endpage 452 en_US
dc.cauo.name SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 0601 Biochemistry and Cell Biology
dc.personcode 102397
dc.percentage 100 en_US
dc.classification.name Biochemistry and Cell Biology en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords cell death pathways ? methionine and choline deficiency ? p53 ? TNF receptors ? insulin-like growth factor-1 ? TRAIL-R killer/DR5 ? mitochondria en_US
dc.description.keywords cell death pathways methionine and choline deficiency p53 TNF receptors insulin-like growth factor-1 TRAIL-R killer/DR5 mitochondria
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
utslib.collection.history Closed (ID: 3)


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