Tilly B C, Gaestel M, Engel K, Edixhoven M J, de Jonge H R
Department of Biochemistry, Cardiovascular Research Institute COEUR, Faculty of Medicine and Health Sciences, Erasmus University, Rotterdam, The Netherlands.
FEBS Lett. 1996 Oct 21;395(2-3):133-6. doi: 10.1016/0014-5793(96)01028-9.
Hypo-osmotic swelling of human Intestine 407 cells leads to a significant increase of intracellular MAPKAP-kinase 2 activity and Hsp27 phosphorylation. Pre-treatment of the cells with the p38 MAP kinase inhibitor SB-203580 blocks this activation, indicating that the hypotonicity-induced activation of MAPKAP kinase 2 is, similarly to that described for hyperosmotic treatment, the result of an activated p38 MAP kinase cascade. The activation of MAPKAP kinase 2 proceeds with kinetics similar to that of one of the first physiological responses of hypo-osmotic treatment, the opening of compensatory Cl- channels. However, inhibition of the p38 MAP kinase cascade does not block the osmo-sensitive anion efflux and, vice versa, activation of p38 MAP kinase by cytokines and anisomycin does not increase the efflux. These results indicate that the p38 MAP kinase cascade is not directly involved in Cl- channel activation but instead may play a role in subsequent cellular repair processes.
人肠407细胞的低渗肿胀导致细胞内MAPKAP激酶2活性和Hsp27磷酸化显著增加。用p38 MAP激酶抑制剂SB - 203580预处理细胞可阻断这种激活，这表明低渗诱导的MAPKAP激酶2激活与高渗处理所描述的情况类似，是活化的p38 MAP激酶级联反应的结果。MAPKAP激酶2的激活动力学与低渗处理的首批生理反应之一——补偿性Cl-通道开放的动力学相似。然而，抑制p38 MAP激酶级联反应并不阻断渗透敏感阴离子外流，反之，细胞因子和茴香霉素对p38 MAP激酶的激活也不会增加外流。这些结果表明，p38 MAP激酶级联反应不直接参与Cl-通道激活，而是可能在随后的细胞修复过程中发挥作用。
