Hepatic gap junctions in the hepatocarcinogen-resistant DRH rat
Hepatic gap junctions in the hepatocarcinogen-resistant DRH rat
复制标题
抗肝癌 DRH 大鼠的肝间隙连接
DOI：
10.1007/s00418-008-0473-0
复制
发表时间：
2008
影响因子：
2.3
通讯作者：
Y. Uchiyama
中科院分区：
文献类型：
--
作者：
T. Gotow;Motoko Shiozaki;T. Higashi;K. Yoshimura;M. Shibata;E. Kominami;Y. Uchiyama
尽管差距连接或连接蛋白（Cx）被认为是肿瘤抑制因子，但它也是肿瘤促进所必需的。因此，我们研究了肝癌耐药（DRH）大鼠的肝脏缝隙连接。具体而言，我们研究了正常条件下以及对肝癌原3′-甲基-4-二甲氨基偶氮苯（3′-MeDAB）的反应中的间隙连接结构和Cx 32表达。形态计量学、免疫组化和免疫印迹显示，在不含3′-MeDAB的基础饲料中，DRH大鼠的肝脏缝隙连接和Cx 32蛋白表达均高于对照组。在含有3′-MeDAB的饲料中，DRH大鼠的缝隙连接和表达的Cx 32显著增加，而DRH大鼠则没有。在这种情况下，Donryu大鼠体重减轻，但DRH大鼠增加了相对肝脏重量。经3′-MeDAB处理后，仅在DRH大鼠肝细胞中的组织蛋白酶D表达显著增加，表明DRH大鼠对3′-MeDAB的敏感性较低。3′-MeDAB处理后，与DRH大鼠相比，Donryu大鼠中丝裂原活化蛋白激酶的丰度降低了更大程度，其中一些成分可能与Cx蛋白磷酸化程度有关。DRH大鼠对致癌的抵抗力可能部分归因于其稳定的缝隙连接，其可以协调代谢偶联以逃避3′-MeDAB毒性。
Although the gap junction or connexin (Cx) is considered to be a tumor-suppressor, it is also required for tumor promotion. Therefore, we examined hepatic gap junctions in hepatocarcinogen-resistant (DRH) rats. Specifically, we investigated gap junction structure and Cx32 expression during normal conditions and in response to a hepatocarcinogen, 3′-methyl-4-dimethylaminoazobenzene (3′-MeDAB). On a basal diet without 3′-MeDAB, hepatic gap junctions and Cx32 protein expression were greater in DRH rats than in control Donryu rats, as evidenced by morphometry, immunohistochemistry and immunoblotting. On a diet containing 3′-MeDAB, gap junctions and expressed Cx32 were increased significantly in Donryu rats, but not in DRH rats. In this condition, Donryu rats lost weight but DRH rats increased relative liver weight. After 3′-MeDAB treatment, cathepsin D expression in hepatocytes was significantly increased only in Donryu rats, indicating that DRH rats were less susceptible to 3′-MeDAB. The abundance of mitogen-activated protein kinase, some constituent of which might be associated with the degree of Cx protein phosphorylation, was reduced to a greater extent in Donryu than in DRH rats after 3′-MeDAB treatment. The resistance of DRH rats to carcinogenesis may be due partially to their stabilized gap junctions, which could coordinate metabolic coupling to evade 3′-MeDAB toxicity.
影响因子：
4.7
作者：
King, TJ;Lampe, PD
通讯作者：
Lampe, PD
多种机制导致大鼠肝脏肿瘤发生过程中间隙连接基因表达的改变。
影响因子：
4
作者：
Neveu,MJ;Hully,JR;Babcock,KL;Hertzberg,EL;Nicholson,BJ;Paul,DL;Pitot,HC
通讯作者：
Pitot,HC
大麻素抑制大鼠肝上皮细胞系中间隙连接细胞间通讯并激活 ERK。
影响因子：
6.4
作者：
Upham,BradL;Rummel,AlisaM;Carbone,JosephM;Trosko,JamesE;Ouyang,Yanli;Crawford,RobertB;Kaminski,NorbertE
通讯作者：
Kaminski,NorbertE