Por favor, use este identificador para citar o enlazar a este item:
http://hdl.handle.net/10261/124734
COMPARTIR / EXPORTAR:
SHARE CORE BASE | |
Visualizar otros formatos: MARC | Dublin Core | RDF | ORE | MODS | METS | DIDL | DATACITE | |
Campo DC | Valor | Lengua/Idioma |
---|---|---|
dc.contributor.author | Win, Sanda | - |
dc.contributor.author | Than, Tinaung | - |
dc.contributor.author | Le, Bao Han | - |
dc.contributor.author | García-Ruiz, Carmen | - |
dc.contributor.author | Fernández-Checa, José C. | - |
dc.contributor.author | Kaplowitz, Neil | - |
dc.date.accessioned | 2015-11-10T10:10:07Z | - |
dc.date.available | 2015-11-10T10:10:07Z | - |
dc.date.issued | 2015-06-01 | - |
dc.identifier | doi: 10.1016/j.jhep.2015.01.032 | - |
dc.identifier | issn: 0168-8278 | - |
dc.identifier.citation | Journal of Hepatology 62(6): 1367-1374 (2015) | - |
dc.identifier.uri | http://hdl.handle.net/10261/124734 | - |
dc.description.abstract | Background & Aims Sustained c-Jun N-terminal kinase (JNK) activation by saturated fatty acids plays a role in lipotoxicity and the pathogenesis of non-alcoholic steatohepatitis (NASH). We have reported that the interaction of JNK with mitochondrial Sab leads to inhibition of respiration, increased reactive oxygen species (ROS), cell death and hepatotoxicity. We tested whether this pathway underlies palmitic acid (PA)-induced lipotoxicity in hepatocytes. Methods Primary mouse hepatocytes (PMH) from adeno-shlacZ or adeno-shSab treated mice and HuH7 cells were used. Results In PMH, PA dose-dependently up to 1 mM stimulated oxygen consumption rate (OCR) due to mitochondrial β-oxidation. At â>4;1.5 mM, PA gradually reduced OCR, followed by cell death. Inhibition of JNK, caspases or treatment with antioxidant butylated hydroxyanisole (BHA) protected PMH against cell death. Sab knockdown or a membrane permeable Sab blocking peptide prevented PA-induced mitochondrial impairment, but inhibited only the late phase of both JNK activation (beyond 4 h) and cell death. In PMH, PA increased p-PERK and its downstream target CHOP, but failed to activate the IRE-1α arm of the UPR. However, Sab silencing did not affect PA-induced PERK activation. Conversely, specific inhibition of PERK prevented JNK activation and cell death, indicating a major role upstream of JNK activation. Conclusions The effect of p-JNK on mitochondria plays a key role in PA-mediated lipotoxicity. The interplay of p-JNK with mitochondrial Sab leads to impaired respiration, ROS production, sustained JNK activation, and apoptosis. © 2015 European Association for the Study of the Liver | - |
dc.description.sponsorship | This work was supported by NIH grants RO1-DK067215 (NK) and RO1-AA014428 (NK), the USC Research Center for Liver Disease (P30-DK48522) Cellular and Tissue Imaging, Cell Separation and Culture, and Analytical/Metabolic/Instrumentation Cores and the Southern California Research Center for Alcoholic Liver and Pancreatic Disease (P30-AA11999) | - |
dc.publisher | European Association for the Study of the Liver | - |
dc.publisher | Elsevier | - |
dc.rights | closedAccess | - |
dc.subject | Apoptosis | - |
dc.subject | Hepatocytes | - |
dc.subject | Mitochondria | - |
dc.subject | Palmitic acid | - |
dc.subject | Reactive oxygen species | - |
dc.title | Sab (Sh3bp5) dependence of JNK mediated inhibition of mitochondrial respiration in palmitic acid induced hepatocyte lipotoxicity. | - |
dc.type | artículo | - |
dc.identifier.doi | 10.1016/j.jhep.2015.01.032 | - |
dc.relation.publisherversion | http://dx.doi.org/10.1016/j.jhep.2015.01.032 | - |
dc.date.updated | 2015-11-10T10:10:09Z | - |
dc.description.version | Peer Reviewed | - |
dc.language.rfc3066 | eng | - |
dc.contributor.funder | National Institutes of Health (US) | - |
dc.relation.csic | Sí | - |
dc.identifier.funder | http://dx.doi.org/10.13039/100000002 | es_ES |
dc.identifier.pmid | 25666017 | - |
dc.type.coar | http://purl.org/coar/resource_type/c_6501 | es_ES |
item.fulltext | No Fulltext | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | artículo | - |
item.cerifentitytype | Publications | - |
item.grantfulltext | none | - |
Aparece en las colecciones: | (IIBB) Artículos |
Ficheros en este ítem:
Fichero | Descripción | Tamaño | Formato | |
---|---|---|---|---|
accesoRestringido.pdf | 15,38 kB | Adobe PDF | Visualizar/Abrir |
CORE Recommender
PubMed Central
Citations
59
checked on 11-abr-2024
SCOPUSTM
Citations
100
checked on 24-abr-2024
WEB OF SCIENCETM
Citations
100
checked on 27-feb-2024
Page view(s)
264
checked on 24-abr-2024
Download(s)
120
checked on 24-abr-2024
Google ScholarTM
Check
Altmetric
Altmetric
Artículos relacionados:
NOTA: Los ítems de Digital.CSIC están protegidos por copyright, con todos los derechos reservados, a menos que se indique lo contrario.