Role of UCP2 Expression after Hepatic Warm Ischemia-Reperfusion in the Rat
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background/Aims: The role of uncoupling protein-2 (UCP2)in the liver is currently unclear. Emerging evidence suggests a relationship between UCP2 and oxidative stress. In the present study, we tested the hypothesis that UCP2 expression in the liver might change during warm ischemia-reperfusion (I/R) according to oxidative stress. Methods: Wistar rats were subjected to 40 (short ischemia) or 90 (long ischemia)minutes of partial lobar ischemia followed by 4 hours of reperfusion. UCP2 expression in the ischemic and nonischemic lobes was assessed using reverse transcription-polymerase chain reaction and immunohistochemistry. Malondialdehyde concentrations in the liver tissue were also compared. Results:Malondialdehyde concentrations in the ischemic lobes were significantly higher in the long ischemia group. In the ischemic lobes of the short ischemia group, UCP2 protein expression was induced in hepatocytes, which did not express the protein prior to treatment, and the expression levels were higher than in the long ischemia group. The intralobular distribution of UCP2 seemed to correlate inversely with that of the necrotic area. UCP2 expression was observed, even in nonischemic lobes with similar intralobular heterogeneity. Conclusions: UCP2 was induced in hepatocytes after warm I/R. Although the primitive role of UCP2 expression may be cytoprotective in nature, its actual protective effect in hepatic I/R may be minimal.
Abstract
Background/Aims: The role of uncoupling protein-2 (UCP2)in the liver is currently unclear. Emerging evidence suggests a relationship between UCP2 and oxidative stress. In the present study, we tested the hypothesis that UCP2 expression in the liver might change during warm ischemia-reperfusion (I/R) according to oxidative stress. Methods: Wistar rats were subjected to 40 (short ischemia) or 90 (long ischemia)minutes of partial lobar ischemia followed by 4 hours of reperfusion. UCP2 expression in the ischemic and nonischemic lobes was assessed using reverse transcription-polymerase chain reaction and immunohistochemistry. Malondialdehyde concentrations in the liver tissue were also compared. Results:Malondialdehyde concentrations in the ischemic lobes were significantly higher in the long ischemia group. In the ischemic lobes of the short ischemia group, UCP2 protein expression was induced in hepatocytes, which did not express the protein prior to treatment, and the expression levels were higher than in the long ischemia group. The intralobular distribution of UCP2 seemed to correlate inversely with that of the necrotic area. UCP2 expression was observed, even in nonischemic lobes with similar intralobular heterogeneity. Conclusions: UCP2 was induced in hepatocytes after warm I/R. Although the primitive role of UCP2 expression may be cytoprotective in nature, its actual protective effect in hepatic I/R may be minimal.
참고문헌 (30)
- Ninomiya M, "The hydroxyl radical scavenger MCI-186 protects the liver from experimental cold ischaemia-reperfusion injury", Br J Surg, 91, pp.184~190 (2004)
- Ninomiya M, "Beneficial effect of MCI-186 on hepatic warm ischemia-reperfusion in the rat", Transplantation, 74, pp.1470~1472 (2002)
- Kumamoto Y, "Kupffer cellindependent acute hepatocellular oxidative stress and decreased bile formation in post-cold-ischemic rat liver", Hepatology, 30, pp.1454~1463 (1999)
- Tanaka J, "Effects of prostaglandin I2, superoxide dismutase, and catalase on ischemia-reperfusion injury in liver transplantation", ASAIO Trans, 36, pp.M600~M603 (1990)
- García-Ruiz C, "Role of oxidative stress generated from the mitochondrial electron transport chain and mitochondrial glutathione status in loss of mitochondrial function and activation of transcription factor nuclear factor-kappa B: studies with isolated mitochondria and rat hepatocytes", Mol Pharmacol, 48, pp.825~834 (1995)
- Enerbäck S, "Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese", Nature, 387, pp.90~94 (1997)
- Fleury C, "Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia", Nat Genet, 15, pp.269~272 (1997)
- Ricquier D, "Molecular studies of the uncoupling protein", FASEB J, 5, pp.2237~2242 (1991)
- Vidal-Puig AJ, "Energy metabolism in uncoupling protein 3 gene knockout mice", J Biol Chem, 275, pp.16258~16266 (2000)
- Echtay KS, "Superoxide activates mitochondrial uncoupling proteins", Nature, 4156, pp.96~99 (2002)
- Arsenijevic D, "Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production", Nat Genet, 26, pp.435~439 (2000)
- liver, "Hepatology", 1999, 677~687
- Yang S, "Mitochondrial adaptations to obesityrelated oxidant stress", Arch Biochem Biophys, 378, pp.259~268 (2000)
- Cortez-Pinto H, "Lipids up-regulate uncoupling protein 2 expression in rat hepatocytes", Gastroenterology, 116, pp.1184~1193 (1999)
- Richard D, "Uncoupling protein 2 in the brain: distribution and function", Biochem Soc Trans, 29(Pt 6), pp.812~817 (2001)
- Larrouy D, "Kupffer cells are a dominant site of uncoupling protein 2 expression in rat liver", Biochem Biophys Res Commun, 235, pp.760~764 (1997)
- Chavin KD, "Obesity induces expression of uncoupling protein-2 in hepatocytes and promotes liver ATP depletion", J Biol Chem, 274, pp.5692~5700 (1999)
- Kawano K, "The beneficial effect of cyclosporine on liver ischemia in rats", Transplantation, 48, pp.759~764 (1989)
- Kimura K, "Induction of uncoupling protein (UCP) 2 in primary cultured hepatocytes", FEBS Lett, 457, pp.75~79 (1999)
- Mueller L, "The induction of the immediate-early-genes Egr-1, PAI-1 and PRL-1 during liver regeneration in surgical models is related to increased portal flow", J Hepatol, 37, pp.606~612 (2002)
- Guerrieri F, "Mitochondrial oxidative alterations following partial hepatectomy", Free Radic Biol Med, 26, pp.34~41 (1999)
- Cortez-Pinto H, "Bacterial lipopolysaccharide induces uncoupling protein-2 expression in hepatocytes by a tumor necrosis factor-alpha-dependent mechanism", Biochem Biophys Res Commun, 251, pp.313~319 (1998)
- Colletti LM, "Role of tumor necrosis factor-alpha in the pathophysiologic alterations after hepatic ischemia", reperfusion injury in the rat, 1990, pp.85, 1936~1943
- Kato Y, "Intralobular heterogeneity of oxidative stress and cell death in ischemia-reperfused rat liver", J Surg Res, 95, pp.99~106 (2001)
- Serviddio G, "Uncoupling protein-2 (UCP2) induces mitochondrial proton leak and increases susceptibility of non-alcoholic steatohepatitis (NASH) liver to ischaemiareperfusion injury", Gut, 57, pp.957~965 (2008)
- Le Minh K, "Uncoupling protein-2 deficient mice are not protected against warm ischemia", reperfusion injury of the liver, 2010, pp.10, ~
- Diehl AM, "Mitochondrial uncoupling: role of uncoupling protein anion carriers and relationship to thermogenesis and weight control “the benefits of losing control”", J Bioenerg Biomembr, 31, pp.493~506 (1999)
- Nègre-Salvayre A, "A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation", FASEB J, 11, pp.809~815 (1997)
- Kuhla A, "Oxidative stressassociated rise of hepatic protein glycation increases inflammatory liver injury in uncoupling protein-2 deficient mice", Lab Invest, 90, pp.1189~1198 (2010)
- Li LX, "Uncoupling protein-2 participates in cellular defense against oxidative stress in clonal beta-cells", Biochem Biophys Res Commun, 282, pp.273~277 (2001)