Regulation of intracellular levels of NAD: A novel role for CD38
Regulation of intracellular levels of NAD: A novel role for CD38
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DOI：
10.1016/j.bbrc.2006.05.042
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发表时间：
2006-07-14
影响因子：
3.1
通讯作者：
Chini, Eduardo N.
中科院分区：
文献类型：
--
作者：
Aksoy, Pinar;White, Thomas A.;Chini, Eduardo N.
烟酰胺腺嘌呤二核苷酸（NAD）在许多细胞功能中起关键作用。除了其在能量代谢中的众所周知的作用外，NAD还在信号转导、衰老和细胞损伤中发挥作用。NAD还参与许多信号转导途径。因此，必须了解控制细胞内NAD水平的机制。然而，迄今为止，调节细胞内NAD水平的机制尚未完全阐明。CD38是一种多功能酶，广泛分布于哺乳动物组织中。CD38被认为是负责合成第二信使的酶。然而，其主要的酶活性是NAD的水解，事实上，每水解100个NAD分子，CD38就会产生一个cADPR分子。迄今为止，尚未探索CD38作为NAD水平调节剂的作用。我们推测CD38是哺乳动物细胞中主要的NAD酶，并且它调节细胞内NAD水平。在目前的研究中，我们检查了野生型和CD38缺陷型小鼠的各种组织中的NAD酶活性和NAD水平。根据我们的假设，我们发现CD 38缺陷小鼠的NAD组织水平比野生型动物高10至20倍。此外，在CD38缺陷小鼠的大多数组织中，质膜、线粒体、肌浆网和细胞核中的NAD酶活性基本上不存在。这些数据支持新的概念，即CD38是细胞NAD水平的主要调节因子。这些发现对于理解调节细胞内NAD水平的机制及其在能量稳态，信号转导和衰老中的作用具有重要意义。(c)2006年爱思唯尔公司All rights reserved.
Nicotinamide adenine dinucleotide (NAD) plays key roles in many cellular functions. In addition to its well-known role in energy metabolism, NAD also plays a role in signal transduction, ageing, and cellular injury. NAD is also involved in many signal transduction pathways. Therefore, it is imperative to understand the mechanisms that control intracellular NAD levels. However, to date, the mechanisms that regulate intracellular levels of NAD have not been completely elucidated. CD38 is a multifunctional enzyme ubiquitously distributed in mammalian tissues. CD38 has been implicated as the enzyme responsible for the synthesis of the second messengers. However, its major enzymatic activity is the hydrolysis of NAD, in fact, CD38 will generate one molecule of cADPR for every 100 molecules of NAD hydrolyzed. To date, the role of CD38 as a modulator of levels of NAD has not been explored. We postulated that CD38 is the major NADase in mammalian cells and that it regulates intracellular NAD levels. In the current studies we examined the NADase activities and NAD levels in a variety of tissues from both wild-type and CD38 deficient mice. In accordance with our hypothesis, we found that tissue levels of NAD in CD38 deficient mice are 10- to 20-fold higher than in wild-type animals. In addition, NADase activity in the plasma membrane, mitochondria, sarcoplasmic reticulum, and nuclei is essentially absent in most tissues from CD38 deficient mice. These data support the novel concept that CD38 is a major regulator of cellular NAD levels. These findings have implications for understanding the mechanisms that regulate intracellular NAD levels and its role in energy homeostasis, signal transduction, and ageing. (c) 2006 Elsevier Inc. All rights reserved.