title: Ischemic preconditioning attenuates ischemia/reperfusion injury in rat steatotic liver: role of heme oxygenase-1-mediated autophagy.
abstract: Steatotic livers are more susceptible to ischemia/reperfusion (I/R) injury, which is ameliorated by ischemic preconditioning (IPC). Autophagy possesses protective action on liver I/R injury and declines in steatotic livers. The aim of this study was to test the hypothesis that the increased susceptibility of steatotic livers to I/R injury was associated with defective hepatic autophagy, which could be restored by IPC via heme oxygenase-1 (HO-1) signaling. Obesity and hepatic steatosis was induced using a high fat diet. Obesity impaired hepatic autophagy activity and decreased hepatic HO-1 expression. Induction of HO-1 restored autophagy activity and inhibited calpain 2 activity. Additionally, suppression of calpain 2 activity also restored autophagy activity. Mitochondrial dysfunction and hepatocellular injury were significantly increased in steatotic livers compared to lean livers in response to I/R injury. This increase in sensitivity to I/R injury was associated with defective hepatic autophagy activity in steatotic livers. IPC increased autophagy and reduced mitochondrial dysfunction and hepatocellular damage in steatotic livers following I/R injury. Furthermore, IPC increased HO-1 expression. Inhibition of HO-1 decreased the IPC-induced autophagy, increased calpain 2 activity and diminished the protective effect of IPC against I/R injury. Inhibition of calpain 2 restored autophagic defect and attenuated mitochondrial dysfunction in steatotic livers after I/R. Collectively, IPC might ameliorate steatotic liver damage and restore mitochondrial function via HO-1-mediated autophagy.
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.|Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Anding
authors.initials: A
authors.lastname: Liu
authors.affiliation: Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Enshuang
authors.initials: E
authors.lastname: Guo
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jiankun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Renlong
authors.initials: R
authors.lastname: Li
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shenpei
authors.initials: S
authors.lastname: Liu
authors.affiliation: Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Jifa
authors.initials: J
authors.lastname: Hu
authors.affiliation: Department of Infectious Diseases, Wuhan General Hospital of Guangzhou Military Command, Wuhan, China.
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Jiang
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Olaf
authors.initials: O
authors.lastname: Dirsch
authors.affiliation: Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, Friedrich-Schiller-University Jena, Jena, Germany.
authors.forename: Uta
authors.initials: U
authors.lastname: Dahmen
authors.affiliation: Department of Biliopancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Anesthesiology, The Fifth Affiliated Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Mingwen
authors.initials: M
authors.lastname: Ouyang
mesh_terms: D000818:Animals; D001343:Autophagy; D000071193:Autophagy-Related Protein 7 / Q000235:genetics / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002478:Cells, Cultured; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism*; D022781:Hepatocytes / Q000201:enzymology* / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008099:Liver / Q000201:enzymology* / Q000473:pathology; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000473:pathology; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection
chemical_list: C561242:Atg7 protein, rat; D006419:Heme Oxygenase (Decyclizing); C491523:Hmox1 protein, rat; D002154:Calpain; C000594975:Capn2 protein, rat; D000071193:Autophagy-Related Protein 7
keywords: autophagy; heme oxygenase-1, Pathology Section; ischemic preconditioning; liver ischemia/reperfusion injury; steatosis