Immenschuh S, Fahimi H D, Baumgart-Vogt E
Institute for Clinical Immunology und Transfusion Medicine, University of Giessen Langhansstr. 7, 35392 Giessen, Germany.
Cell Mol Biol (Noisy-le-grand). 2005 Oct 3;51(5):471-7.
Heme oxygenase (HO)-1, the inducible isoform of the rate-limiting enzyme of heme degradation, and peroxiredoxin (Prx) I, a thioredoxin-dependent peroxidase, are multifunctional antioxidant stress proteins which are coordinately up-regulated by oxidative stress in cell cultures. HO-1 and Prx I exhibit a different hepatic cellular and subcellular localization. Here, a distinct expression pattern of the two genes was confirmed by in situ hybridization of normal rat liver. Moreover, expression of the HO-1 and Prx I genes was determined in a model of acutely damaged rat liver which was elicited by application of a single dose of carbon tetrachloride (CCl4). The mRNA levels of the HO-1 and Prx I genes were induced in whole livers of CCl4-treated rats with differential kinetics as determined by Northern blot analysis. While HO-1 mRNA was induced up to 48 hr, Prx I exhibited a maximum level of mRNA after 12 hr of treatment with CCl4. CCl4-dependent oxidative stress led to a focal increase of perivenous HO-1 positive liver cells with simultaneous loss of Prx I immunoreactivity. Taken together, the complementary hepatic gene expression pattern of HO-1 and Prx I in response to oxidative stress may suggest a functional interplay of these antioxidant genes.
血红素加氧酶（HO）-1是血红素降解限速酶的诱导型同工酶，而过氧化物酶（Prx）I是一种硫氧还蛋白依赖性过氧化物酶，它们都是多功能抗氧化应激蛋白，在细胞培养中可被氧化应激协同上调。HO-1和Prx I在肝脏细胞和亚细胞中的定位不同。在此，通过正常大鼠肝脏的原位杂交证实了这两个基因的独特表达模式。此外，在单次注射四氯化碳（CCl4）诱导的急性损伤大鼠肝脏模型中，测定了HO-1和Prx I基因的表达。通过Northern印迹分析确定，HO-1和Prx I基因的mRNA水平在CCl4处理的大鼠全肝中以不同的动力学被诱导。HO-1 mRNA在48小时内被诱导，而Prx I在CCl4处理12小时后mRNA水平达到最高。CCl4依赖性氧化应激导致肝小叶中央静脉周围HO-1阳性肝细胞局部增加，同时Prx I免疫反应性丧失。综上所述，HO-1和Prx I在肝脏中对氧化应激的互补基因表达模式可能表明这些抗氧化基因之间存在功能相互作用。
