Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion
- PMID: 27521978
- DOI: 10.1016/j.taap.2016.08.010
Role of necroptosis in autophagy signaling during hepatic ischemia and reperfusion
Abstract
Ischemia and reperfusion (I/R) is a complex phenomenon involving massive inflammation and cell death. Necroptosis refers to a newly described cell death as "programmed necrosis" that is controlled by receptor-interacting protein kinase (RIP) 1 and RIP3, which is involved in the pathogenesis of several inflammatory diseases. Autophagy is an essential cytoprotective system that is rapidly activated in response to various stimuli and involves crosstalk between different modes of cell death and inflammation. In this study, we investigated pattern changes in necroptosis and its role in autophagy signaling during hepatic I/R. Male C57BL/6 mice were subjected to 60min of ischemia followed by 3h reperfusion. Necrostatin-1 (Nec-1, a necroptosis inhibitor; 1.65mg/kg) was administered intraperitoneally 5min before reperfusion. Hepatic I/R significantly increased the level of RIP3, phosphorylated RIP1 and RIP3 protein expression, and RIP1/RIP3 necrosome formation, which were attenuated by Nec-1. I/R also significantly increased serum levels of alanine aminotransferase, tumor necrosis factor-α, and interleukin-6, which were attenuated by Nec-1. Meanwhile, hepatic I/R activated autophagy and mitophagy, as evidenced by increased LC3-II, PINK1, and Parkin, and decreased sequestosome 1/p62 protein expression. Nec-1 attenuated these changes and attenuated the increased levels of autophagy-related protein (ATG) 3, ATG7, Rab7, and cathepsin B protein expression during hepatic I/R. Moreover, hepatic I/R activated the extracellular signal-regulated kinase (ERK) pathway, and Nec-1 attenuated this increase. Taken together, our findings suggest that necroptosis contributes to hepatic damage during I/R, which induces autophagy via ERK activation.
Keywords: Autophagy; Ischemia/reperfusion; Liver; Necroptosis; Necrostatin-1.
Copyright © 2016 Elsevier Inc. All rights reserved.
Similar articles
-
Genipin protects d-galactosamine and lipopolysaccharide-induced hepatic injury through suppression of the necroptosis-mediated inflammasome signaling.Eur J Pharmacol. 2017 Oct 5;812:128-137. doi: 10.1016/j.ejphar.2017.07.024. Epub 2017 Jul 11. Eur J Pharmacol. 2017. PMID: 28709622
-
RIP1-Dependent Programmed Necrosis is Negatively Regulated by Caspases During Hepatic Ischemia-Reperfusion.Shock. 2015 Jul;44(1):72-6. doi: 10.1097/SHK.0000000000000371. Shock. 2015. PMID: 26009812
-
Metformin mediates cardioprotection against aging-induced ischemic necroptosis.Aging Cell. 2020 Feb;19(2):e13096. doi: 10.1111/acel.13096. Epub 2020 Jan 14. Aging Cell. 2020. PMID: 31944526 Free PMC article.
-
Crosstalk between apoptosis, necrosis and autophagy.Biochim Biophys Acta. 2013 Dec;1833(12):3448-3459. doi: 10.1016/j.bbamcr.2013.06.001. Epub 2013 Jun 13. Biochim Biophys Acta. 2013. PMID: 23770045 Review.
-
Decoding cell death signals in liver inflammation.J Hepatol. 2013 Sep;59(3):583-94. doi: 10.1016/j.jhep.2013.03.033. Epub 2013 Apr 6. J Hepatol. 2013. PMID: 23567086 Review.
Cited by
-
Responses of hepatic sinusoidal cells to liver ischemia-reperfusion injury.Front Cell Dev Biol. 2023 Apr 4;11:1171317. doi: 10.3389/fcell.2023.1171317. eCollection 2023. Front Cell Dev Biol. 2023. PMID: 37082623 Free PMC article. Review.
-
Liver Ischemia and Reperfusion Induce Periportal Expression of Necroptosis Executor pMLKL Which Is Associated With Early Allograft Dysfunction After Transplantation.Front Immunol. 2022 May 17;13:890353. doi: 10.3389/fimmu.2022.890353. eCollection 2022. Front Immunol. 2022. PMID: 35655777 Free PMC article.
-
The role of MLKL in Hepatic Ischemia-Reperfusion Injury of Alcoholic Steatotic Livers.Int J Biol Sci. 2022 Jan 1;18(3):1096-1106. doi: 10.7150/ijbs.67533. eCollection 2022. Int J Biol Sci. 2022. PMID: 35173541 Free PMC article.
-
Liver ischaemia-reperfusion injury: a new understanding of the role of innate immunity.Nat Rev Gastroenterol Hepatol. 2022 Apr;19(4):239-256. doi: 10.1038/s41575-021-00549-8. Epub 2021 Nov 26. Nat Rev Gastroenterol Hepatol. 2022. PMID: 34837066 Review.
-
Dual Lactate Clearance in the Viability Assessment of Livers Donated After Circulatory Death With Ex Situ Normothermic Machine Perfusion.Transplant Direct. 2021 Nov 17;7(12):e789. doi: 10.1097/TXD.0000000000001243. eCollection 2021 Dec. Transplant Direct. 2021. PMID: 34805491 Free PMC article.
Publication types
MeSH terms
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous