Schliess F, Heinrich S, Häussinger D
Clinic for Gastroenterology, Hepatology, and Infectiology, Heinrich-Heine-Universität, Düsseldorf, Germany.
Arch Biochem Biophys. 1998 Mar 1;351(1):35-40. doi: 10.1006/abbi.1997.0517.
The action of hyperosmotic stress on the MAP kinase phosphatase MKP-1 mRNA expression was studied in H4IIE rat hepatoma cells. Hyperosmotic (405 mosmol/L) challenge of the cells led to a transient expression of MKP-1 mRNA, which was maximal after 6-8 h and disappeared completely after 24 h. Hyperosmotic MKP-1 mRNA induction was preceded by a transient activation of the MAP kinases Erk-1, Erk-2, and JNK-2, which were not prerequisite for MKP-1 mRNA accumulation. However, the hyperosmolarity-induced MKP-1 mRNA expression was sensitive to antioxidants and to inhibition of p38 by SB203580. A reduced sensitivity of Erk-1/Erk-2 to other stimuli was found after prolonged hyperosmotic exposure. The data are consistent with a hyperosmolarity-induced MKP-1 expression via reactive oxygen intermediates and p38, which may participate in the termination of MAP kinase activation and contribute to desensitization of the MAP kinases after prolonged hyperosmotic exposure of the cells.
在H4IIE大鼠肝癌细胞中研究了高渗应激对丝裂原活化蛋白激酶磷酸酶MKP-1 mRNA表达的作用。对细胞进行高渗（405 mosmol/L）刺激导致MKP-1 mRNA短暂表达，在6-8小时后达到最大值，并在24小时后完全消失。高渗诱导MKP-1 mRNA之前，丝裂原活化蛋白激酶Erk-1、Erk-2和JNK-2会短暂激活，但它们不是MKP-1 mRNA积累的先决条件。然而，高渗诱导的MKP-1 mRNA表达对抗氧化剂和SB203580抑制p38敏感。长时间高渗暴露后，发现Erk-1/Erk-2对其他刺激的敏感性降低。这些数据与通过活性氧中间体和p38诱导的高渗性MKP-1表达一致，这可能参与丝裂原活化蛋白激酶激活的终止，并有助于细胞长时间高渗暴露后丝裂原活化蛋白激酶的脱敏。
