Loetscher P, Alvarez-Gonzalez R, Althaus F R
Proc Natl Acad Sci U S A. 1987 Mar;84(5):1286-9. doi: 10.1073/pnas.84.5.1286.
In mammalian cells, NAD+ serves a dual role as a respiratory coenzyme and as a substrate for the posttranslational poly(ADP-ribose) modification of chromatin proteins, catalyzed by the nuclear enzyme poly(ADP-ribose) polymerase [NAD+ ADP-ribosyltransferase, EC 2.4.2.30]. Biological evidence strongly suggests that poly(ADP-ribosyl)ation modulates chromatin functions, although the precise molecular mechanisms involved have not yet been elucidated. Here we describe conditions for the rapid uptake of exogenously supplied NAD+ by living hepatocytes in primary monolayer culture. Raising the intracellular NAD+ concentration by 70% caused a 5-fold increase of chromatin-bound poly(ADP-ribose). We conclude that the constitutive level of posttranslational poly(ADP-ribose) modifications of chromatin proteins in mammalian cells is related to the availability of NAD+, which varies in different physiological and pathological states. We propose that poly-(ADP-ribose) may serve a hitherto unrecognized function by signaling altered metabolic conditions to the chromatin and thus modulate its functions in tune with changing metabolic states.
在哺乳动物细胞中，NAD+具有双重作用，既是呼吸辅酶，又是由核酶聚（ADP-核糖）聚合酶[NAD+ ADP-核糖基转移酶，EC 2.4.2.30]催化的染色质蛋白翻译后聚（ADP-核糖）修饰的底物。生物学证据有力地表明，聚（ADP-核糖基）化调节染色质功能，尽管其中涉及的精确分子机制尚未阐明。在此，我们描述了原代单层培养的活肝细胞快速摄取外源供应的NAD+的条件。将细胞内NAD+浓度提高70%会导致与染色质结合的聚（ADP-核糖）增加5倍。我们得出结论，哺乳动物细胞中染色质蛋白翻译后聚（ADP-核糖）修饰的组成水平与NAD+的可用性有关，NAD+在不同的生理和病理状态下会有所变化。我们提出，聚（ADP-核糖）可能通过向染色质发出代谢条件改变的信号来发挥一种迄今未被认识的功能，从而根据代谢状态的变化调节其功能。
