培养细胞中腺苷酸环化酶活性、3':5'-环磷酸腺苷磷酸二酯酶活性、3':5'-环磷酸腺苷水平与细胞生长之间的相互关系。
Interrelationship between adenylate cyclase activity, adenosine 3':5' cyclic monophosphate phosphodiesterase activity, adenosine 3':5' cyclic monophosphate levels, and growth of cells in culture.
作者信息
Anderson W B, Russell T R, Carchman R A, Pastan I
出版信息
Proc Natl Acad Sci U S A. 1973 Dec;70(12):3802-5. doi: 10.1073/pnas.70.12.3802.
To investigate how cell population density influences the intracellular concentration of cyclic AMP we have measured adenylate cyclase and cyclic AMP phosphodiesterase activities and cyclic AMP levels at various stages of cell density in normal rat-kidney (NRK) cells, which exhibit contact-inhibition of growth, and in normal chick-embryo fibroblasts (CEF), which do not show contact inhibition of growth under our conditions. Until NRK cells reach confluency, both activities increase with increasing cell population and cyclic AMP levels are low. As NRK cells reach confluency, cyclic AMP phosphodiesterase activity decreases somewhat whereas adenylate cyclase activity continues to rise. This increase in synthetic ability is accompanied by the increase in cyclic AMP levels which occurs in these cells at confluency. In CEF grown in 5% serum where density-dependent inhibition of growth is not observed, both adenylate cyclase and cyclic AMP phosphodiesterase activities increase proportionately with increasing cell population density. No significant alteration occurs in the ratio between these two enzyme activities and no change is observed in cyclic AMP levels. The NaF-stimulated activity in NRK cells increases with increasing cell density until the cells reach confluency; thereafter the NaF-stimulated activity remains constant. In contrast, the NaF-stimulated activity observed in CEF does not vary appreciably between light and heavy density. The observed changes in the enzymes of cyclic AMP metabolism accurately reflect the changes in cyclic AMP concentration as a function of cell population density. The data indicate that these two enzyme activities respond to increasing cell density to elicit a rise in intracellular cyclic AMP levels. The elevated cyclic AMP levels are thought to be involved in the regulation of cellular growth rate and the mediation of contact inhibition of growth.
为了研究细胞群体密度如何影响细胞内环磷酸腺苷（cAMP）的浓度，我们测定了正常大鼠肾（NRK）细胞和正常鸡胚成纤维细胞（CEF）在不同细胞密度阶段的腺苷酸环化酶和环磷酸腺苷磷酸二酯酶活性以及环磷酸腺苷水平。NRK细胞表现出生长接触抑制，而在我们的实验条件下，CEF细胞不表现出接触抑制。在NRK细胞达到汇合状态之前，这两种酶的活性均随细胞群体数量的增加而增加，且环磷酸腺苷水平较低。当NRK细胞达到汇合状态时，环磷酸腺苷磷酸二酯酶活性略有下降，而腺苷酸环化酶活性继续上升。合成能力的这种增加伴随着这些细胞在汇合时环磷酸腺苷水平的升高。在5%血清中生长的CEF细胞中，未观察到密度依赖性生长抑制，腺苷酸环化酶和环磷酸腺苷磷酸二酯酶活性均随细胞群体密度的增加而成比例增加。这两种酶活性之间的比例没有显著变化，环磷酸腺苷水平也没有改变。NRK细胞中氟化钠刺激的活性随细胞密度的增加而增加，直至细胞达到汇合状态；此后，氟化钠刺激的活性保持恒定。相比之下，在CEF细胞中观察到的氟化钠刺激的活性在低密度和高密度之间没有明显变化。观察到的环磷酸腺苷代谢酶的变化准确反映了环磷酸腺苷浓度随细胞群体密度的变化。数据表明，这两种酶活性对细胞密度增加的反应会引起细胞内环磷酸腺苷水平的升高。环磷酸腺苷水平的升高被认为参与了细胞生长速率的调节以及生长接触抑制的介导。
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