The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.
The CD38 glycohydrolase and the NAD sink: implications for pathological conditions.
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DOI：
10.1152/ajpcell.00451.2021
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发表时间：
2022-02
期刊：
影响因子：
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通讯作者：
J. D. Zeidler;K. Hogan;Guilherme Agorrody;Thais R. Peclat;Sonu Kashyap;K. Kanamori;Lilian S. Gomez;Delaram Z Mazdeh;G. Warner;Katie L. Thompson;Claudia C S Chini;E. Chini
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文献类型：
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作者：
J. D. Zeidler;K. Hogan;Guilherme Agorrody;Thais R. Peclat;Sonu Kashyap;K. Kanamori;Lilian S. Gomez;Delaram Z Mazdeh;G. Warner;Katie L. Thompson;Claudia C S Chini;E. Chini
烟酰胺腺嘌呤二核苷酸（NAD）在几种氧化还原反应中充当辅因子，并且是许多非氧化还原酶的底物。NAD是多种细胞过程的基础，包括能量代谢、细胞信号传导和表观遗传学。NAD稳态似乎对健康和长寿至关重要，其失调与多种疾病有关。NAD代谢是动态的，通过合成和降解来维持。酶CD38是NAD的主要消耗酶之一，是NAD稳态的关键组成部分。大多数CD38位于质膜中，其催化结构域面向细胞外环境，可能是为了控制NAD的全身水平。几种细胞类型表达CD38，但其表达主要在能够浸润器官和组织的内皮细胞和免疫细胞上。在这里，我们回顾了CD38在健康和疾病中的潜在作用，并假设CD38失调导致NAD稳态变化的方式，并有助于多种疾病的病理生理学。事实上，在动物模型中，感染性疾病、自身免疫性疾病、纤维化、代谢性疾病和年龄相关性疾病（包括癌症、心脏病和神经变性）的发展与改变的CD38酶活性相关。这些条件中的许多在CD38缺陷型小鼠中或通过阻断CD38 NAD酶活性而被改变。在CD38似乎发挥作用的疾病中，CD38依赖性NAD下降通常是病理生理学的共同特征。因此，了解CD 38对NAD稳态的失调可能为治疗人类疾病开辟新的途径。
Nicotinamide adenine dinucleotide (NAD) acts as a cofactor in several oxidation-reduction reactions and is a substrate for a number of non-redox enzymes. NAD is fundamental to a variety of cellular processes including energy metabolism, cell signaling, and epigenetics. NAD homeostasis appears to be of paramount importance to healthspan and longevity and its dysregulation is associated with multiple diseases. NAD metabolism is dynamic and maintained by synthesis and degradation. The enzyme CD38, one of the main NAD-consuming enzymes, is a key component of NAD homeostasis. The majority of CD38 is localized in the plasma membrane with its catalytic domain facing the extracellular environment, likely for the purpose of controlling systemic levels of NAD. Several cell types express CD38, but its expression predominates on endothelial cells and immune cells capable of infiltrating organs and tissues. Here we review potential roles of CD38 in health and disease and postulate ways in which CD38 dysregulation causes changes in NAD homeostasis and contributes to the pathophysiology of multiple conditions. Indeed, in animal models the development of infectious diseases, autoimmune disorders, fibrosis, metabolic diseases, and age-associated diseases including cancer, heart disease, and neurodegeneration are associated with altered CD38 enzymatic activity. Many of these conditions are modified in CD38 deficient mice or by blocking CD38 NADase activity. In diseases in which CD38 appears to play a role, CD38-dependent NAD decline is often a common denominator of pathophysiology. Thus, understanding dysregulation of NAD homeostasis by CD38 may open new avenues for the treatment of human diseases.