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Medical Molecular Morphology
Published in: Medical Molecular Morphology 2/2019

Open Access 01-06-2019 | Review

Protective role of heme oxygenase-1 in fatty liver ischemia–reperfusion injury

Authors: Shaowei Li, Masayuki Fujino, Terumi Takahara, Xiao-Kang Li

Published in: Medical Molecular Morphology | Issue 2/2019

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Abstract

Ischemia–reperfusion (IR) injury is a kind of injury resulting from the restoration of the blood supply after blood vessel closure during liver transplantation and is the main cause of graft failure. The pathophysiological mechanisms of hepatic IR include a variety of oxidative stress responses. Hepatic IR is characterized by ischemia and hypoxia inducing oxidative stress, immune response and apoptosis. Fat-denatured livers are also used as donors due to the lack of liver donors. Fatty liver is less tolerant to IR than normal liver. Heme oxygenase (HO) is an enzyme that breaks down hemoglobin to bilirubin, ferrous iron and carbon monoxide (CO). Inducible HO subtype HO-1 is an important protective molecule in mammalian cells used to improve acute and chronic liver injury owing to its characteristic anti-inflammatory and anti-apoptotic qualities. HO-1 degrades heme, and its reaction product CO has been shown to reduce hepatic IR injury and increase the survival rate of grafts. As an induced form of HO, HO-1 also exerts a protective effect against liver IR injury and may be useful as a new strategy of ameliorating this kind of damage. This review summarizes the protective effects of HO-1 in liver IR injury, especially in fatty liver.
Literature
1.
2.
3.
4.
5.
6.
7.
Van Sweringen HL, Sakai N, Quillin RC, Bailey J, Schuster R, Blanchard J et al (2013) Roles of hepatocyte and myeloid CXC chemokine receptor-2 in liver recovery and regeneration after ischemia/reperfusion in mice. Hepatology 57(1):331–338. https://​doi.​org/​10.​1002/​hep.​26049 (PubMed PMID: 22961770; PubMed Central PMCID: PMCPMC3540195) CrossRefPubMed
8.
9.
10.
11.
Katada K, Bihari A, Mizuguchi S, Yoshida N, Yoshikawa T, Fraser DD et al (2010) Carbon monoxide liberated from CO-releasing molecule (CORM-2) attenuates ischemia/reperfusion (I/R)-induced inflammation in the small intestine. Inflammation 33(2):92–100. https://​doi.​org/​10.​1007/​s10753-009-9162-y (PubMed PMID: 19842024) CrossRef
12.
13.
14.
Palladini G, Ferrigno A, Rizzo V, Tarantola E, Bertone V, Freitas I et al (2014) Lung matrix metalloproteinase activation following partial hepatic ischemia/reperfusion injury in rats. Sci World J 2014:867548. https://​doi.​org/​10.​1155/​2014/​867548 (PubMed PMID: 24592193; PubMed Central PMCID: PMCPMC3921999) CrossRef
15.
Kuboki S, Shin T, Huber N, Eismann T, Galloway E, Schuster R et al (2008) Hepatocyte signaling through CXC chemokine receptor-2 is detrimental to liver recovery after ischemia/reperfusion in mice. Hepatology 48(4):1213–1223. https://​doi.​org/​10.​1002/​hep.​22471 (PubMed PMID: 18688883; PubMed Central PMCID: PMCPMC2695827) CrossRefPubMed
16.
Mochizuki A, Pace A, Rockwell CE, Roth KJ, Chow A, O’Brien KM et al (2014) Hepatic stellate cells orchestrate clearance of necrotic cells in a hypoxia-inducible factor-1alpha-dependent manner by modulating macrophage phenotype in mice. J Immunol 192(8):3847–3857. https://​doi.​org/​10.​4049/​jimmunol.​1303195 (PubMed PMID: 24639359; PubMed Central PMCID: PMCPMC4538924) CrossRefPubMed
17.
Duffield JS, Forbes SJ, Constandinou CM, Clay S, Partolina M, Vuthoori S et al (2005) Selective depletion of macrophages reveals distinct, opposing roles during liver injury and repair. J Clin Investig 115(1):56–65 (PubMed PMID: 15630444; PubMed Central PMCID: PMCPMC539199) CrossRefPubMedPubMedCentral
18.
19.
20.
Bak SU, Kim S, Hwang HJ, Yun JA, Kim WS, Won MH et al (2017) Heme oxygenase-1 (HO-1)/carbon monoxide (CO) axis suppresses RANKL-induced osteoclastic differentiation by inhibiting redox-sensitive NF-kappaB activation. BMB Rep 50(2):103–108 (PubMed PMID: 28088947; PubMed Central PMCID: PMCPMC5342874) CrossRef
21.
22.
23.
24.
25.
Andres MM, Luszczki JJ (2004) Modified western blot technique in fast detection of heme oxygenase (HO-1/HO-2) in various tissues and organs of experimental animals. Ann Univ Mariae Curie Sklodowska Med 59(2):298–302 (PubMed PMID: 16146096) PubMed
26.
27.
28.
29.
30.
31.
32.
33.
34.
35.
36.
37.
38.
39.
40.
41.
42.
43.
44.
Kolios G, Valatas V, Kouroumalis E (2006) Role of Kupffer cells in the pathogenesis of liver disease. World J Gastroenterol 12(46):7413–7420 (PubMed PMID: 17167827; PubMed Central PMCID: PMCPMC4087584) CrossRef
45.
Li J, Li RJ, Lv GY, Liu HQ (2015) The mechanisms and strategies to protect from hepatic ischemia-reperfusion injury. Eur Rev Med Pharmacol Sci 19(11):2036–2047 (PubMed PMID: 26125267)
46.
Shuh M, Bohorquez H, Loss GE Jr, Cohen AJ (2013) Tumor necrosis factor-alpha: life and death of hepatocytes during liver ischemia/reperfusion injury. Ochsner J 13(1):119–30 (PubMed PMID: 23531747; PubMed Central PMCID: PMCPMC3603175)
47.
Cutrn JC, Perrelli MG, Cavalieri B, Peralta C, Rosell Catafau J, Poli G (2002) Microvascular dysfunction induced by reperfusion injury and protective effect of ischemic preconditioning. Free Radic Biol Med 33(9):1200–1208 (PubMed PMID: 12398928) CrossRef
48.
49.
50.
51.
52.
Seki E, Tsutsui H, Nakano H, Tsuji N, Hoshino K, Adachi O et al (2001) Lipopolysaccharide-induced IL-18 secretion from murine Kupffer cells independently of myeloid differentiation factor 88 that is critically involved in induction of production of IL-12 and IL-1beta. J Immunol 166(4):2651–2657 (PubMed PMID: 11160328) CrossRef
53.
Zeng Z, Huang HF, Chen MQ, Song F, Zhang YJ (2010) Heme oxygenase-1 protects donor livers from ischemia/reperfusion injury: the role of Kupffer cells. World J Gastroenterol 16(10):1285–1292 (PubMed PMID: 20222175; PubMed Central PMCID: PMCPMC2839184) CrossRef
54.
Devey L, Ferenbach D, Mohr E, Sangster K, Bellamy CO, Hughes J et al (2009) Tissue-resident macrophages protect the liver from ischemia reperfusion injury via a heme oxygenase-1-dependent mechanism. Mol Ther 17(1):65–72. https://​doi.​org/​10.​1038/​mt.​2008.​237 (PubMed PMID: 19002167; PubMed Central PMCID: PMCPMC2834991) CrossRefPubMed
55.
Takagi T, Naito Y, Uchiyama K, Suzuki T, Hirata I, Mizushima K et al (2011) Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice. Dig Dis Sci 56(6):1663–1671. https://​doi.​org/​10.​1007/​s10620-010-1484-y (PubMed PMID: 21086163) CrossRef
56.
57.
Kato H, Amersi F, Buelow R, Melinek J, Coito AJ, Ke B et al (2001) Heme oxygenase-1 overexpression protects rat livers from ischemia/reperfusion injury with extended cold preservation. Am J Transplant 1(2):121–128 (PubMed PMID: 12099359) CrossRef
58.
Coito AJ, Buelow R, Shen XD, Amersi F, Moore C, Volk HD et al (2002) Heme oxygenase-1 gene transfer inhibits inducible nitric oxide synthase expression and protects genetically fat Zucker rat livers from ischemia-reperfusion injury. Transplantation 74(1):96–102 (PubMed PMID: 12134106) CrossRefPubMed
59.
60.
61.
62.
63.
64.
65.
66.
Harlan JM, Winn RK (2002) Leukocyte-endothelial interactions: clinical trials of anti-adhesion therapy. Crit Care Med 30(5 Suppl):S214–S219 (PubMed PMID: 12004238)
67.
68.
69.
70.
71.
72.
73.
Feldstein AE, Canbay A, Angulo P, Taniai M, Burgart LJ, Lindor KD et al (2003) Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology 125(2):437–443 (PubMed PMID: 12891546) CrossRef
74.
75.
76.
Day CP, James OF (1998) Steatohepatitis: a tale of two “hits”? Gastroenterology 114(4):842–845 (PubMed PMID: 9547102) CrossRef
77.
78.
79.
80.
Pessayre D, Fromenty B, Mansouri A (2004) Mitochondrial injury in steatohepatitis. Eur J Gastroenterol Hepatol 16(11):1095–1105 (PubMed PMID: 15489566) CrossRef
81.
Sookoian S, Rosselli MS, Gemma C, Burgueno AL, Fernandez Gianotti T, Castano GO et al (2010) Epigenetic regulation of insulin resistance in nonalcoholic fatty liver disease: impact of liver methylation of the peroxisome proliferator-activated receptor gamma coactivator 1alpha promoter. Hepatology 52(6):1992–2000. https://​doi.​org/​10.​1002/​hep.​23927 (PubMed PMID: 20890895) CrossRefPubMed
82.
83.
84.
85.
Swift C, Garner JP (2012) Non-operative management of liver trauma. J R Army Med Corps 158(2):85–95 (PubMed PMID: 22860496) CrossRefPubMed
86.
Jaeschke H (2002) Reperfusion injury after warm ischemia or cold storage of the liver: role of apoptotic cell death. Transpl Proc 34(7):2656–2658 (PubMed PMID: 12431564) CrossRef
87.
88.
89.
90.
91.
92.
93.
94.
95.
Kennedy JC, Pottier RH (1992) Endogenous protoporphyrin IX, a clinically useful photosensitizer for photodynamic therapy. J Photochem Photobiol B 14(4):275–292. (PubMed PMID: 1403373) CrossRef
96.
97.
98.
99.
100.
Ambati RR, Phang SM, Ravi S, Aswathanarayana RG (2014) Astaxanthin: sources, extraction, stability, biological activities and its commercial applications—a review. Mar Drugs 12(1):128–152. https://​doi.​org/​10.​3390/​md12010128 (PubMed PMID: 24402174; PubMed Central PMCID: PMCPMC3917265) CrossRef
101.
102.
103.
104.
105.
106.
107.
108.
109.
110.
111.
112.
113.
114.
115.
116.
117.
Jin Q, Zhu K, Cui W, Xie Y, Han B, Shen W (2013) Hydrogen gas acts as a novel bioactive molecule in enhancing plant tolerance to paraquat-induced oxidative stress via the modulation of heme oxygenase-1 signalling system. Plant Cell Environ 36(5):956–969. https://​doi.​org/​10.​1111/​pce.​12029 (PubMed PMID: 23094798) CrossRefPubMed
118.
Tamaki N, Orihuela-Campos RC, Fukui M, Ito HO (2016) Hydrogen-rich water intake accelerates oral palatal wound healing via activation of the Nrf2/antioxidant defense pathways in a rat model. Oxid Med Cell Longev 2016:5679040. https://​doi.​org/​10.​1155/​2016/​5679040 (PubMed PMID: 26798423; PubMed Central PMCID: PMCPMC4699099) CrossRefPubMed
119.
120.
Metadata
Title
Protective role of heme oxygenase-1 in fatty liver ischemia–reperfusion injury
Authors
Shaowei Li
Masayuki Fujino
Terumi Takahara
Xiao-Kang Li
Publication date
01-06-2019
Publisher
Springer Japan
Published in
Medical Molecular Morphology / Issue 2/2019
Print ISSN: 1860-1480
Electronic ISSN: 1860-1499
DOI
https://doi.org/10.1007/s00795-018-0205-z

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