Machida T, Higashi K, Ogawara H
Department of Biochemistry, Meiji College of Pharmacy, Tokyo, Japan.
J Antibiot (Tokyo). 1995 Oct;48(10):1076-80. doi: 10.7164/antibiotics.48.1076.
The effects of cochlioquinone A, isolated from Drechslera sacchari, were studied in vitro and in vivo. This compound specifically inhibited diacylglycerol kinase activity with Ki = 3.1 microM. The kinetics revealed that cochlioquinone A inhibited diacylglycerol kinase in competition with ATP, and non-competitively with diacylglycerol. The compound inhibited neither protein kinase C, epidermal growth factor receptor-associated protein tyrosine kinase, nor phospholipase C. Cochlioquinone A reduced the concentration of phosphatidic acid in T cell lymphoma with a half maximal concentration of 3 microM, and simultaneously augmented the phosphorylation of 80 kDa protein, a known substrate of protein kinase C. The degree of the phosphorylation of 80 kDa protein in the presence of cochlioquinone A was similar to that in the presence of phorbol myristate acetate (0.1 microgram/ml). These results demonstrate that cochlioquinone A is a specific inhibitor of diacylglycerol kinase, which regulates the activity of protein kinase C.
对从甘蔗长蠕孢菌中分离出的辅酶Q A的作用进行了体外和体内研究。该化合物特异性抑制二酰基甘油激酶活性，其抑制常数Ki = 3.1微摩尔。动力学研究表明，辅酶Q A与ATP竞争抑制二酰基甘油激酶，与二酰基甘油非竞争性抑制。该化合物既不抑制蛋白激酶C、表皮生长因子受体相关蛋白酪氨酸激酶，也不抑制磷脂酶C。辅酶Q A可使T细胞淋巴瘤中磷脂酸浓度降低，半数最大浓度为3微摩尔，同时增强80 kDa蛋白的磷酸化，80 kDa蛋白是蛋白激酶C的已知底物。在辅酶Q A存在下80 kDa蛋白的磷酸化程度与在佛波醇肉豆蔻酸酯乙酸盐（0.1微克/毫升）存在下相似。这些结果表明，辅酶Q A是二酰基甘油激酶的特异性抑制剂，可调节蛋白激酶C的活性。
