Kuhara Makihiko, Wang Jingshu, Flores Maria Jolina, Qiao Zhiwei, Koizumi Yukio, Koyota Souichi, Taniguchi Naoyuki, Sugiyama Toshihiro
Department of Biochemistry, Osaka University Graduate School of Medicine, Yamadaoka, Suita, Osaka, Japan.
Biomed Res. 2011 Apr;32(2):111-7. doi: 10.2220/biomedres.32.111.
We examined age-related changes in the protein expression of carbonic anhydrase III (CAIII) in livers of Long-Evans with a cinnamon-like color (LEC) rats using an agouti color (LEA) rats as controls. The levels of the protein of CAIII in the liver of LEC male rats increased before 20 weeks of age, at the stage of acute hepatitis, and were decreased at 54 weeks of age, while those of CAIII in the liver of LEA male rats were highly expressed at all ages. In the normal LEA rats, CAIII showed sexual dimorphism. The level of CAIII in LEA male rat liver relative to female was four times higher. On the other hand, young LEC rat (at 4-12 weeks) showed a higher protein level of CAIII than LEA rats, and then decreased during development of hepatitis. CAIII mRNA also decreased in the LEC rat liver during hepatocarcinogenesis. The level of CAIII in the tumor region was lower than that in the tumor-free region. Immunohistochemical analysis showed that glutathione S-transferase P (GST-P) was positive and CAIII was negative in the precancerous region. The expression of CAIII was suppressed in cancerous lesions in hepatoma-bearing LEC rat liver compared to uninvolved surrounding tissues. These results indicated that suppression of CAIII accompanied hepatocarcinogenesis and it is a secondary consequence of the high copper levels in the liver.
我们以刺鼠色（LEA）大鼠作为对照，研究了肉桂色（LEC）Long-Evans大鼠肝脏中碳酸酐酶III（CAIII）蛋白表达的年龄相关变化。LEC雄性大鼠肝脏中CAIII蛋白水平在20周龄前、急性肝炎阶段升高，在54周龄时降低，而LEA雄性大鼠肝脏中的CAIII蛋白在所有年龄段均高表达。在正常LEA大鼠中，CAIII表现出性别二态性。LEA雄性大鼠肝脏中CAIII的水平相对于雌性高出四倍。另一方面，年轻的LEC大鼠（4 - 12周龄）肝脏中CAIII蛋白水平高于LEA大鼠，然后在肝炎发展过程中降低。在LEC大鼠肝癌发生过程中，其肝脏中CAIII mRNA也减少。肿瘤区域中CAIII的水平低于无肿瘤区域。免疫组织化学分析显示，癌前区域谷胱甘肽S-转移酶P（GST-P）呈阳性而CAIII呈阴性。与未受累的周围组织相比，携带肝癌的LEC大鼠肝脏癌性病变中CAIII的表达受到抑制。这些结果表明，CAIII的抑制伴随着肝癌发生，并且这是肝脏中高铜水平的继发后果。
