Impairment of PGC-1 alpha up-regulation enhances nitrosative stress in the liver during acute pancreatitis in obese mice
PublisherMDPI, Basel, Switzerland
10.3390/antiox9090887Antioxidants 9.9 (2020): 887
Funded byThis work was supported by Grant GV/2019/153 from the Generalitat Valenciana, Conselleria d’Educació, Investigació, Cultura I Esport .
SubjectsAcute pancreatitis; Liver; Nitrosative stress; Obesity; PGC-1α; Biología y Biomedicina / Biología
Rights© 2020 The Authors
Esta obra está bajo una Licencia Creative Commons Atribución 4.0 Internacional.
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.
Google Scholar:Rius-Pérez, Sergio - Torres-Cuevas, Isabel - Monsalve, María - Miranda, Francisco J. - Pérez, Salvador
This item appears in the following Collection(s)
Showing items related by title, author, creator and subject.
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
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, David; Csiszár, Katalin; Portillo, Francisco García Del; Peinado, Héctor; Palacios, José Luis; Cano, Amparo
Fernblock® Upregulates NRF2 Antioxidant Pathway and Protects Keratinocytes from PM2.5-Induced Xenotoxic Stress Delgado-Wicke, Pablo; Rodríguez-Luna, Azahara; Ikeyama, Yoshifumi; Honma, Yoichi; Kume, Toshiaki; Gutiérrez, María; Lorrio, Silvia; Juarranz, Ángeles; González, Salvador