Impairment of PGC-1 alpha up-regulation enhances nitrosative stress in the liver during acute pancreatitis in obese mice
Editor
MDPI, Basel, SwitzerlandFecha de edición
2020-09-19Cita
10.3390/antiox9090887
Antioxidants 9.9 (2020): 887
ISSN
2076-3921DOI
10.3390/antiox9090887Financiado por
This work was supported by Grant GV/2019/153 from the Generalitat Valenciana, Conselleria d’Educació, Investigació, Cultura I Esport .Versión del editor
http://doi.org/10.3390/antiox9090887Materias
Acute pancreatitis; Liver; Nitrosative stress; Obesity; PGC-1α; Biología y Biomedicina / BiologíaDerechos
© 2020 The AuthorsResumen
Acute pancreatitis is an inflammatory process of the pancreatic tissue that often leads to distant organ dysfunction. Although liver injury is uncommon in acute pancreatitis, obesity is a risk factor for the development of hepatic complications. The aim of this work was to evaluate the role of PGC-1α in inflammatory response regulation in the liver and its contribution to the detrimental effect of obesity on the liver during acute pancreatitis. For this purpose, we induced acute pancreatitis by cerulein in not only wild-type (WT) and PGC-1α knockout (KO) mice, but also in lean and obese mice. PGC-1α levels were up-regulated in the mice livers with pancreatitis. The increased PGC-1α levels were bound to p65 to restrain its transcriptional activity toward Nos2. Lack of PGC-1α favored the assembly of the p65/phospho-STAT3 complex, which promoted Nos2 expression during acute pancreatitis. The increased transcript Nos2 levels and the pro-oxidant liver status caused by the down-regulated expression of the PGC-1α-dependent antioxidant genes enhanced nitrosative stress and decreased energy charge in the livers of the PGC-1α KO mice with pancreatitis. It is noteworthy that the PGC-1α levels lowered in the obese mice livers, which increased the Nos2 mRNA expression and protein nitration levels and decreased energy charge during pancreatitis. In conclusion, obesity impairs PGC-1α up-regulation in the liver to cause nitrosative stress during acute pancreatitis.
Lista de ficheros
Google Scholar:Rius-Pérez, Sergio
-
Torres-Cuevas, Isabel
-
Monsalve, María
-
Miranda, Francisco J.
-
Pérez, Salvador
Lista de colecciones del ítem
Registros relacionados
Mostrando ítems relacionados por título, autor, creador y materia.
-
Lysyl oxidase-like 2 (LOXL2), a new regulator of cell polarity required for metastatic dissemination of basal-like breast carcinomas
Moreno Bueno, Gema; Salvador, Fernando; Martín, Alberto Lancina; Floristán, Alfredo; Cuevas, Eva P.; Santos, Vanesa L.; Montes, Amalia; Morales, Saleta; Castilla, María Ángeles; Rojo-Sebastián, Alejandro; Martínez, Alejandra Nacarino; Hardisson Hernáez, David Alonso; Csiszár, Katalin; Portillo Pérez, Francisco; Peinado, Héctor; Palacios, José Luis; Cano, Amparo
2011-09-01 -
Liver growth factor (LGF) upregulates frataxin protein expression and reduces oxidative stress in friedreich’s ataxia transgenic mice
Calatrava-Ferreras, Lucía; Gonzalo-Gobernado, Rafael; Reimers, Diana; Herranz, Antonio S.; Casarejos, María J.; Jiménez-Escrig, Adriano; Regadera, Javier; Velasco-Martín, Juan Pedro; Vallejo-Muñoz, Manuela; Díaz-Gil, Juan José; Bazán, Eulalia
2016-12-09