1. DSpace at MEDIU
  2. Harvested articles مقالات مستوردة من مؤسسات وجامعات عالمية
  3. Digital Csic
Please use this identifier to cite or link to this item: http://dspace.mediu.edu.my:8181/xmlui/handle/10261/5351
Full metadata record
DC FieldValueLanguage
dc.creatorMarí, Montserrat-
dc.creatorColell Riera, Anna-
dc.creatorMorales, Albert-
dc.creatorGarcía-Ruiz, Carmen-
dc.creatorFernández-Checa, José C.-
dc.creatorVarela-Nieto, Isabel-
dc.creatorPañeda, Covadonga-
dc.date2008-06-26T07:28:28Z-
dc.date2008-06-26T07:28:28Z-
dc.date2004-03-15-
dc.date.accessioned2017-01-31T01:53:02Z-
dc.date.available2017-01-31T01:53:02Z-
dc.identifierJournal of Clinical Investigation 113(6): 895–904 (2004)-
dc.identifier0021-9738-
dc.identifierhttp://hdl.handle.net/10261/5351-
dc.identifier10.1172/JCI200419852-
dc.identifier.urihttp://dspace.mediu.edu.my:8181/xmlui/handle/10261/5351-
dc.descriptionS-adenosyl-L-methionine (SAM) is synthesized by methionine adenosyltransferases (MATs). Ablation of the liver-specific MAT1A gene results in liver neoplasia and sensitivity to oxidant injury. Here we show that acidic sphingomyelinase (ASMase) mediates the downregulation of MAT1A by TNF-α. The levels of MAT1A mRNA as well as MAT I/III protein decreased in cultured rat hepatocytes by in situ generation of ceramide from exogenous human placenta ASMase. Hepatocytes lacking the ASMase gene (ASMase–/–) were insensitive to TNF-α but were responsive to exogenous ASMase-induced downregulation of MAT1A. In an in vivo model of lethal hepatitis by TNF-α, depletion of SAM preceded activation of caspases 8 and 3, massive liver damage, and death of the mice. In contrast, minimal hepatic SAM depletion, caspase activation, and liver damage were seen in ASMase–/– mice. Moreover, therapeutic treatment with SAM abrogated caspase activation and liver injury, thus rescuing ASMase+/+ mice from TNF-α–induced lethality. Thus, we have demonstrated a new role for ASMase in TNF-α–induced liver failure through downregulation of MAT1A, and maintenance of SAM may be useful in the treatment of acute and chronic liver diseases.-
dc.descriptionThe work presented was supported in part by the Research Center for Liver and Pancreatic Diseases, P50 AA 11999; and grant 1R21 AA014135-01, funded by the US National Institute on Alcohol Abuse and Alcoholism; Plan Nacional de I+D grants SAF01-2118, SAF2002-3564, and SAF2003-04974; and Red Temática de Investigación Cooperativa G03/015 and Red de Centros C03/02, supported by Instituto de Salud Carlos III. We want to thank Susana Nuñez for expert technical assistance and genotyping of ASMase–/– mice. M. Marí and A. Morales are Ramón y Cajal investigators.-
dc.descriptionPeer reviewed-
dc.format3641378 bytes-
dc.formatapplication/pdf-
dc.languageeng-
dc.publisherAmerican Society for Clinical Investigation-
dc.relationhttp://dx.doi.org/10.1172/JCI200419852-
dc.rightsopenAccess-
dc.titleAcidic sphingomyelinase downregulates the liver-specific methionine adenosyltransferase 1A, contributing to tumor necrosis factor–induced lethal hepatitis-
dc.typeArtículo-
Appears in Collections:Digital Csic

Files in This Item:
There are no files associated with this item.
Show simple item record


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.