Matsumoto A, Hanayama R, Nakamura M, Suzuki K, Fujii J, Tatsumi H, Taniguchi N
Department of Biochemistry, Osaka University Medical School, Suita, Japan.
Free Radic Res. 1998 Apr;28(4):383-91. doi: 10.3109/10715769809070807.
We have examined changes in the expression of heme oxygenase-1 (HO-1), an inducible isoform and HO-2, a constitutive isoform, in the liver of Long-Evans with a Cinnamon-like color (LEC) rat, a mutant strain which spontaneously develops acute hepatitis and hepatoma. HO-1 expression was highly enhanced in the LEC rat livers with jaundice, and then decreased slightly, but overall remained at a higher level than in the Long-Evans with Agouti color (LEA) control rats, as judged by Northern blotting analysis of the whole liver extract. The high expression of HO-1 in the LEC rat liver was, however, not due to the actual cancer lesion but, rather, due to the surrounding uninvolved tissues including hepatocytes. Immunohistochemical analysis also supported this conclusion. Among normal tissues, the expression of HO-1 but not HO-2 was high in only the spleen of both LEC and LEA rats. The high expression observed in the stage of acute hepatitis and hepatoma stages in the LEC rat is probably due to the oxidative stress caused by the accumulation of free copper and free iron levels which has been reported earlier by our group (Suzuki et al., Carcinogenesis, 1993, 14, 1881-1884 and Koizumi et al., Free Radical Research, in press) as well as by free heme levels. The inflammatory cytokines produced by the surrounding tissue at the hepatoma stage would also be expected to play a role in the induction mechanism. The physiological relevance of HO-1 induction might be an adaptive response to oxidative stress and vasodilatory effect of carbon monoxide on sinusoidal circulation.
我们检测了血红素加氧酶-1（HO-1，一种诱导型同工酶）和HO-2（一种组成型同工酶）在具有肉桂样毛色的Long-Evans（LEC）大鼠肝脏中的表达变化。LEC大鼠是一种自发发生急性肝炎和肝癌的突变品系。通过对全肝提取物的Northern印迹分析判断，HO-1在黄疸型LEC大鼠肝脏中的表达显著增强，随后略有下降，但总体仍高于具有刺豚鼠毛色的Long-Evans（LEA）对照大鼠。然而，LEC大鼠肝脏中HO-1的高表达并非由于实际的癌灶，而是由于包括肝细胞在内的周围未受累组织。免疫组织化学分析也支持这一结论。在正常组织中，HO-1而非HO-2仅在LEC和LEA大鼠的脾脏中高表达。在LEC大鼠急性肝炎和肝癌阶段观察到的高表达可能是由于游离铜和游离铁水平的积累以及游离血红素水平引起的氧化应激，这一点我们团队之前已有报道（Suzuki等人，《癌变》，1993年，14卷，1881 - 1884页；Koizumi等人，《自由基研究》，即将发表），肝癌阶段周围组织产生的炎性细胞因子预计也会在诱导机制中发挥作用。HO-1诱导的生理相关性可能是对氧化应激的适应性反应以及一氧化碳对肝血窦循环的血管舒张作用。
