Cytoplasmic Fine Granular Expression of 8-hydroxydeoxyguanosine Reflects Early Mitochondrial Oxidative DNA Damage in Nonalcoholic Fatty Liver Disease
Cytoplasmic Fine Granular Expression of 8-hydroxydeoxyguanosine Reflects Early Mitochondrial Oxidative DNA Damage in Nonalcoholic Fatty Liver Disease
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DOI：
10.1097/pai.0b013e31803156d5
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发表时间：
2007-12
影响因子：
1.6
通讯作者：
K. Nomoto;K. Tsuneyama;Hiroyuki Takahashi;Y. Murai;Y. Takano
中科院分区：
文献类型：
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作者：
K. Nomoto;K. Tsuneyama;Hiroyuki Takahashi;Y. Murai;Y. Takano
为了阐明氧化应激在非酒精性脂肪性肝病中的可能作用，应用免疫组织化学方法研究了8-羟基脱氧鸟苷(8-OHdG)在非酒精性脂肪性肝炎(NASH)和脂肪变性中的表达。8-OHdG是DNA氧化损伤的良好标志。在双重免疫染色中，胞浆内细颗粒8-OHdG的表达被认为反映了8-OHdG阳性的线粒体DNA对氧化应激的影响。脂肪变性8例中，4例为胞浆8-OHdG，1例为胞核8-OHdG，1例胞浆和胞核均为8-OHdG。相反，8-OHdG在NASH中的表达频率更高(12/13，92%)。8-OHdG仅在胞浆呈细小颗粒状表达(1/13例，8%)，仅在胞核表达(6/13例，46%)，胞浆与胞核同时表达(5/13例，38%)。巨噬细胞线粒体也有强烈的8-OHdG表达。我们认为，8-OHdG在细胞质中的表达呈细小颗粒状，反映了NASH和脂肪变性时肝细胞线粒体DNA的氧化损伤。我们在此提出，细胞质8-OHdG的评估可能是早期非酒精性脂肪性肝病事件的敏感诊断标记物。
To clarify the possible role of oxidative stress in hepatocytes in nonalcoholic fatty liver disease, the hepatic expression of 8-hydroxydeoxyguanosine (8-OHdG), a good marker of oxidative DNA damage, was immunohistochemically investigated in nonalcoholic steatohepatitis (NASH) and steatosis. In double immunostaining, the cytoplasmic fine granular 8-OHdG expression was considered to reflect 8-OHdG–positive mitochondrial DNA affecting oxidation stress. In steatosis, 4 of 8 cases showed cytoplasmic 8-OHdG, 1 case showed nuclear 8-OHdG and 1 case showed both cytoplasmic and nuclear 8-OHdG. In contrast, 8-OHdG expression was more frequently detected in NASH (12 of 13 cases, 92%). Immunoreactivity for 8-OHdG was observed only in the cytoplasm with a fine granular pattern (1 of 13 cases, 8%), only in the nucleus (6 of 13 cases, 46%), and in both the cytoplasm and the nucleus (5 of 13 cases, 38%). Megamitochondria also exhibited 8-OHdG intensely. We indicate that 8-OHdG expression in the cytoplasm with a fine granular pattern reflects oxidative damage to the mitochondrial DNA of hepatocytes in both NASH and steatosis. We propose herein that the evaluation of cytoplasmic 8-OHdG may be a sensitive diagnostic marker of early nonalcoholic fatty liver disease events.