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

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dc.contributor.author Farrell, Geoffrey en_US
dc.contributor.author Larter, C en_US
dc.contributor.author Hou, J en_US
dc.contributor.author Zhang, R en_US
dc.contributor.author Yeh, M en_US
dc.contributor.author Williams, J en_US
dc.contributor.author Pena, A en_US
dc.contributor.author Francisco, R en_US
dc.contributor.author Osvath, S en_US
dc.contributor.author Brooling, J en_US
dc.contributor.author Teoh, N en_US
dc.contributor.author Sedger, Lisa en_US
dc.contributor.editor en_US
dc.date.accessioned 2011-02-07T06:24:06Z
dc.date.available 2011-02-07T06:24:06Z
dc.date.issued 2009 en_US
dc.identifier 2009005245 en_US
dc.identifier.citation Farrell Geoffrey et al. 2009, 'Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression.', The Asia Pacific Association for Gastroenterology, vol. 24, no. 3, pp. 443-452. en_US
dc.identifier.issn 0815-9319 en_US
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. en_US
dc.language en_US
dc.publisher The Asia Pacific Association for Gastroenterology en_US
dc.relation.isbasedon http://dx.doi.org/10.1111/j.1440-1746.2009.05785.x en_US
dc.title Apoptosis in experimental NASH is associated with p53 activation and TRAIL receptor expression. en_US
dc.parent Journal of Gastroenterology and Hepatology en_US
dc.journal.volume 24 en_US
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 060100 en_US
dc.personcode 0000049500 en_US
dc.personcode 0000062209 en_US
dc.personcode 0000062210 en_US
dc.personcode 0000062211 en_US
dc.personcode 0000062212 en_US
dc.personcode 0000062213 en_US
dc.personcode 0000062214 en_US
dc.personcode 0000062215 en_US
dc.personcode 0000062216 en_US
dc.personcode 0000062217 en_US
dc.personcode 0000062218 en_US
dc.personcode 102397 en_US
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.staffid 102397 en_US

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