Regulation of heme oxygenase expression by alcohol, hypoxia and oxidative stress.
Regulation of heme oxygenase expression by alcohol, hypoxia and oxidative stress.
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DOI：
10.4331/wjbc.v2.i12.252
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发表时间：
2011-12-26
期刊：
影响因子：
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通讯作者：
Harrison-Findik, Duygu Dee
中科院分区：
文献类型：
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作者：
Gerjevic, Lisa Nicole;Lu, Sizhao;Harrison-Findik, Duygu Dee
目的：研究急性和慢性酒精暴露对脑、肝和十二指肠血红素加氧酶（HO）的影响.方法：采用野生型C57 BL/6小鼠、锰超氧化物歧化酶（MnSOD）活性降低的杂合型Sod 2基因敲除小鼠和肝脏特异性ARNT基因敲除小鼠，研究酒精诱导的氧化应激和缺氧的作用.对于急性酒精暴露，在饮用水中给予乙醇1周。对小鼠进行常规或含乙醇的Lieber De Carli液体饮食4周的慢性酒精研究。HO表达通过实时定量聚合酶链反应和Western blotting.Results分析：慢性酒精暴露下调HO-1在脑中的表达，但上调它在野生型小鼠的十二指肠。它没有改变肝脏HO-1的表达，也没有HO-2在脑，肝或十二指肠的表达。相反，急性酒精暴露降低了野生型小鼠肝脏HO-1和HO-2的表达，以及十二指肠HO-2的表达。ARNT（+/-）小鼠肝脏HO-1表达的减少被消除。急性酒精暴露的Sod 2（+/-）小鼠肝脏HO-1和HO-2表达或脑HO-2表达没有任何变化。酒精抑制Sod 2（+/-）小鼠脑HO-1和十二指肠HO-2的表达，但增加十二指肠HO-1的表达。总的来说，这些研究结果表明，急性和慢性酒精暴露调节HO表达的组织特异性的方式。长期酒精暴露会改变大脑和十二指肠的HO表达，但不会改变肝脏的HO表达。然而，急性酒精暴露抑制肝脏HO-1和HO-2，也十二指肠HO-2express.CONCLUSION：肝脏HO表达的抑制急性酒精诱导的缺氧可能在酒精性肝病进展的早期阶段发挥作用。
AIM: To study the effect of both acute and chronic alcohol exposure on heme oxygenases (HOs) in the brain, liver and duodenum.METHODS: Wild-type C57BL/6 mice, heterozygous Sod2 knockout mice, which exhibit attenuated manganese superoxide dismutase activity, and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia. For acute alcohol exposure, ethanol was administered in the drinking water for 1 wk. Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies. HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.RESULTS: Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice. It did not alter liver HO-1 expression, nor HO-2 expression in the brain, liver or duodenum. In contrast, acute alcohol exposure decreased both liver HO-1 and HO-2 expression, and HO-2 expression in the duodenum of wild-type mice. The decrease in liver HO-1 expression was abolished in ARNT(+/-) mice. Sod2(+/-) mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression. However, alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2(+/-) mice. Collectively, these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner. Chronic alcohol exposure alters brain and duodenal, but not liver HO expression. However, acute alcohol exposure inhibits liver HO-1 and HO-2, and also duodenal HO-2 expression.CONCLUSION: The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.