TNF-alpha modulates hepatic Na+-K+ ATPase activity via PGE2 and EP2 receptors.
TNF-alpha modulates hepatic Na+-K+ ATPase activity via PGE2 and EP2 receptors.
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发表时间：
2007
影响因子：
2.9
通讯作者：
S. Kreydiyyeh;Sarah Riman;M. Serhan;Ari Kassardjian
中科院分区：
文献类型：
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作者：
S. Kreydiyyeh;Sarah Riman;M. Serhan;Ari Kassardjian
在Sprague-Dawley大鼠和HepG 2细胞中研究了TNF-α对肝Na（+）-K（+）ATP酶的影响。给大鼠腹腔注射TNF-α，4 h后分离肝脏，测定Na（+）-K（+）ATP酶活性和蛋白表达。细胞因子引起ATP酶的显著下调和其活性的降低。这种作用在吲哚美辛（一种考克斯酶抑制剂）存在下消失，并且向动物注射PGE 2模仿TNF-α的作用。当用细胞因子或前列腺素处理HepG 2细胞时，再次出现TNF和PGE 2对泵的观察到的体内作用。不同EP受体激动剂和拮抗剂的应用表明，PGE 2的作用是通过EP 2受体介导的。结论是TNF-α诱导肝细胞产生PGE 2，PGE 2又通过激活EP 2受体降低Na（+）-K（+）ATP酶的活性和蛋白表达。
The effect of TNF-alpha on liver Na(+)-K(+) ATPase was studied in Sprague-Dawley rats and in HepG2 cells. TNF-alpha was injected intraperitoneally to rats and 4h later the liver was isolated and the activity and protein expression of hepatic Na(+)-K(+) ATPase studied. The cytokine caused a significant down-regulation of the ATPase and a decrease in its activity. This effect disappeared in presence of indomethacin, an inhibitor of COX enzymes, and PGE2 injected to the animals imitated the effect of TNF-alpha. The observed in vivo effects of TNF and PGE2 on the pump appeared again when HepG2 cells were treated with the cytokine or the prostaglandin. The application of different agonist and antagonist to EP receptors showed that the effect of PGE2 is mediated via EP2 receptors. It was concluded that TNF-alpha induces in hepatocytes, PGE2 production which in turn reduces the activity and protein expression of the Na(+)-K(+) ATPase by activating EP2 receptors.