Kumar S, Becker G, Prasad K N
Cancer Res. 1975 Jan;35(1):82-7.
The regulation of cyclic adenosine 3:5-monophosphate (cyclic AMP) phosphodiesterase activity in homogenates of malignant and cyclic AMP-induced "differentiated" neuroblastoma cells was studied. Neuroblastoma cells of at least three mouse and one human clone had both the low (2 to 4 muM) and the high (66 to 106 muM) Km phosphodiesterase. In cyclic AMP-induced differentiated cells the values of Km were decreased, whereas the values of Vmax appeared to be slightly increased. Magnesium and manganese stimulated phosphodiesterase activity. Calcium, zinc, copper, mercury, ethylenediaminetetraacetic acid, and imidazole completely inhibited phosphodiesterase activity in malignant cells, whereas the above agents, except ethylenediaminetetraacetic acid, only partially inhibited enzyme activity in differentiated cells. Ethylenediaminetetraacetic acid completely reduced phosphodiesterase activity in differentiated cells. The pH optimum for phosphodiesterase activity was about 8 in both malignant and differentiated cells. The present studies show that the values of Km and Vmax and the sensitivity of phosphodiesterase activity to divalent ions change in cyclic AMP-induced differentiated neuroblastoma cells, and therefore we propose that the reverse may be true during malignant transformation of nerve cells.
研究了恶性神经母细胞瘤细胞及环磷酸腺苷（cAMP）诱导的“分化”神经母细胞瘤细胞匀浆中环磷酸腺苷3':5'-单磷酸（环磷酸腺苷）磷酸二酯酶活性的调节。至少三个小鼠克隆和一个人类克隆的神经母细胞瘤细胞同时具有低Km（2至4μM）和高Km（66至106μM）的磷酸二酯酶。在cAMP诱导的分化细胞中，Km值降低，而Vmax值似乎略有增加。镁和锰刺激磷酸二酯酶活性。钙、锌、铜、汞、乙二胺四乙酸和咪唑完全抑制恶性细胞中的磷酸二酯酶活性，而上述试剂（乙二胺四乙酸除外）仅部分抑制分化细胞中的酶活性。乙二胺四乙酸完全降低分化细胞中的磷酸二酯酶活性。恶性细胞和分化细胞中磷酸二酯酶活性的最适pH约为8。目前的研究表明，cAMP诱导的分化神经母细胞瘤细胞中，磷酸二酯酶的Km和Vmax值以及其对二价离子的敏感性发生了变化，因此我们推测在神经细胞恶性转化过程中情况可能相反。
