Ohoka Y, Nakai Y, Mukai M, Iwata M
Department of Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan.
Biochem Biophys Res Commun. 1993 Dec 15;197(2):916-21. doi: 10.1006/bbrc.1993.2566.
Glucocorticoids induce apoptosis in murine T cell hybridomas. It was inhibited by okadaic acid and calyculin A, potent inhibitors of protein phosphatase 1 and 2A, but not by 1-norokadaone, a structural analog of okadaic acid without phosphatase inhibitory activity. The inhibitory effect of okadaic acid was significant even when it was added 9 h after the start of the culture. Okadaic acid did not prevent either the translocation of glucocorticoid receptor from the cytoplasm to the nucleus or the induction of luciferase activity in the T cell hybridoma transfected with a plasmid containing the luciferase gene under the control of glucocorticoid response elements. These results indicate that protein dephosphorylation is an essential step for glucocorticoid-induced apoptosis in T cell hybridomas, and that the step is at the late stage of the apoptotic process.
糖皮质激素可诱导小鼠T细胞杂交瘤发生凋亡。它受到冈田酸和花萼海绵诱癌素A（蛋白磷酸酶1和2A的强效抑制剂）的抑制，但不受1-去甲冈田酸（一种无磷酸酶抑制活性的冈田酸结构类似物）的抑制。即使在培养开始9小时后添加冈田酸，其抑制作用仍然显著。冈田酸既不阻止糖皮质激素受体从细胞质向细胞核的转位，也不阻止在转染了含有受糖皮质激素反应元件控制的荧光素酶基因的质粒的T细胞杂交瘤中荧光素酶活性的诱导。这些结果表明，蛋白质去磷酸化是糖皮质激素诱导T细胞杂交瘤凋亡的一个必要步骤，且该步骤处于凋亡过程的后期。
