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Ischemic preconditioning protects against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy.
Crit Care Med. 2014 Dec; 42(12):e762-71.CC

Abstract

OBJECTIVES

Ischemic preconditioning exerts a protective effect in hepatic ischemia/reperfusion injury. The exact mechanism of ischemic preconditioning action remains largely unknown. Recent studies suggest that autophagy plays an important role in protecting against ischemia/reperfusion injury. However, the role of autophagy in ischemic preconditioning-afforded protection and its regulatory mechanisms in liver ischemia/reperfusion injury remain poorly understood. This study was designed to determine whether ischemic preconditioning could protect against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy.

DESIGN

Laboratory investigation.

SETTING

University animal research laboratory.

SUBJECTS

Male inbred Lewis rats and C57BL/6 mice.

INTERVENTIONS

Ischemic preconditioning was produced by 10 minutes of ischemia followed by 10 minutes of reperfusion prior to 60 minutes of ischemia. In a rat model of hepatic ischemia/reperfusion injury, rats were pretreated with wortmannin or rapamycin to evaluate the contribution of autophagy to the protective effects of ischemic preconditioning. Heme oxygenase-1 was inhibited with tin protoporphyrin IX. In a mouse model of hepatic ischemia/reperfusion injury, autophagy or heme oxygenase-1 was inhibited with vacuolar protein sorting 34 small interfering RNA or heme oxygenase-1 small interfering RNA, respectively.

MEASUREMENTS AND MAIN RESULTS

Ischemic preconditioning ameliorated liver ischemia/reperfusion injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines, and less severe ischemia/reperfusion-associated histopathologic changes. Ischemic preconditioning treatment induced autophagy activation, as indicated by an increase of LC3-II, degradation of p62, and accumulation of autophagic vacuoles in response to ischemia/reperfusion injury. When ischemic preconditioning-induced autophagy was inhibited with wortmannin in rats or vacuolar protein sorting 34-specific small interfering RNA in mice, liver ischemia/reperfusion injury was worsened, whereas rapamycin treatment increased autophagy and mimicked the protective effects of ischemic preconditioning. Furthermore, ischemic preconditioning increased heme oxygenase-1 expression. The inhibition of heme oxygenase-1 with tin protoporphyrin IX in rats or heme oxygenase-1-specific small interfering RNA in mice decreased ischemic preconditioning-induced autophagy and diminished the protective effects of ischemic preconditioning against ischemia/reperfusion injury.

CONCLUSIONS

Ischemic preconditioning protects against liver ischemia/reperfusion injury, at least in part, via heme oxygenase-1-mediated autophagy.

Authors+Show Affiliations

1Experimental Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. 2Experimental Transplantation Surgery, Department of General, Visceral and Vascular Surgery, University Hospital of Jena, Friedrich-Schiller-University Jena, Jena, Germany. 3Department of Pathophysiology, Anhui Medical University, Hefei, China. 4Institute for Pathology, University Hospital of Jena, Friedrich-Schiller-University Jena, Jena, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25402296

Citation

Liu, Anding, et al. "Ischemic Preconditioning Protects Against Liver Ischemia/reperfusion Injury Via Heme Oxygenase-1-mediated Autophagy." Critical Care Medicine, vol. 42, no. 12, 2014, pp. e762-71.
Liu A, Fang H, Wei W, et al. Ischemic preconditioning protects against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy. Crit Care Med. 2014;42(12):e762-71.
Liu, A., Fang, H., Wei, W., Dirsch, O., & Dahmen, U. (2014). Ischemic preconditioning protects against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy. Critical Care Medicine, 42(12), e762-71. https://doi.org/10.1097/CCM.0000000000000659
Liu A, et al. Ischemic Preconditioning Protects Against Liver Ischemia/reperfusion Injury Via Heme Oxygenase-1-mediated Autophagy. Crit Care Med. 2014;42(12):e762-71. PubMed PMID: 25402296.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Ischemic preconditioning protects against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy. AU - Liu,Anding, AU - Fang,Haoshu, AU - Wei,Weiwei, AU - Dirsch,Olaf, AU - Dahmen,Uta, PY - 2014/11/18/entrez PY - 2014/11/18/pubmed PY - 2015/1/24/medline SP - e762 EP - 71 JF - Critical care medicine JO - Crit. Care Med. VL - 42 IS - 12 N2 - OBJECTIVES: Ischemic preconditioning exerts a protective effect in hepatic ischemia/reperfusion injury. The exact mechanism of ischemic preconditioning action remains largely unknown. Recent studies suggest that autophagy plays an important role in protecting against ischemia/reperfusion injury. However, the role of autophagy in ischemic preconditioning-afforded protection and its regulatory mechanisms in liver ischemia/reperfusion injury remain poorly understood. This study was designed to determine whether ischemic preconditioning could protect against liver ischemia/reperfusion injury via heme oxygenase-1-mediated autophagy. DESIGN: Laboratory investigation. SETTING: University animal research laboratory. SUBJECTS: Male inbred Lewis rats and C57BL/6 mice. INTERVENTIONS: Ischemic preconditioning was produced by 10 minutes of ischemia followed by 10 minutes of reperfusion prior to 60 minutes of ischemia. In a rat model of hepatic ischemia/reperfusion injury, rats were pretreated with wortmannin or rapamycin to evaluate the contribution of autophagy to the protective effects of ischemic preconditioning. Heme oxygenase-1 was inhibited with tin protoporphyrin IX. In a mouse model of hepatic ischemia/reperfusion injury, autophagy or heme oxygenase-1 was inhibited with vacuolar protein sorting 34 small interfering RNA or heme oxygenase-1 small interfering RNA, respectively. MEASUREMENTS AND MAIN RESULTS: Ischemic preconditioning ameliorated liver ischemia/reperfusion injury, as indicated by lower serum aminotransferase levels, lower hepatic inflammatory cytokines, and less severe ischemia/reperfusion-associated histopathologic changes. Ischemic preconditioning treatment induced autophagy activation, as indicated by an increase of LC3-II, degradation of p62, and accumulation of autophagic vacuoles in response to ischemia/reperfusion injury. When ischemic preconditioning-induced autophagy was inhibited with wortmannin in rats or vacuolar protein sorting 34-specific small interfering RNA in mice, liver ischemia/reperfusion injury was worsened, whereas rapamycin treatment increased autophagy and mimicked the protective effects of ischemic preconditioning. Furthermore, ischemic preconditioning increased heme oxygenase-1 expression. The inhibition of heme oxygenase-1 with tin protoporphyrin IX in rats or heme oxygenase-1-specific small interfering RNA in mice decreased ischemic preconditioning-induced autophagy and diminished the protective effects of ischemic preconditioning against ischemia/reperfusion injury. CONCLUSIONS: Ischemic preconditioning protects against liver ischemia/reperfusion injury, at least in part, via heme oxygenase-1-mediated autophagy. SN - 1530-0293 UR - https://www.unboundmedicine.com/medline/citation/25402296/Ischemic_preconditioning_protects_against_liver_ischemia/reperfusion_injury_via_heme_oxygenase_1_mediated_autophagy_ L2 - https://dx.doi.org/10.1097/CCM.0000000000000659 DB - PRIME DP - Unbound Medicine ER -