The NAD+/NADH redox state in astrocytes: Independent control of the NAD+ and NADH content
The NAD+/NADH redox state in astrocytes: Independent control of the NAD+ and NADH content
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DOI：
10.1002/jnr.22638
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发表时间：
2011-12
影响因子：
4.2
通讯作者：
Franziska Wilhelm;J. Hirrlinger
中科院分区：
文献类型：
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作者：
Franziska Wilhelm;J. Hirrlinger
细胞内氧化还原状态由几种氧化还原对建立，如NAD+/NADH和NADP+/NADPH和谷胱甘肽。这种氧化还原状态是细胞代谢和功能的关键决定因素。星形胶质细胞是脑代谢和脑能量供应的重要细胞群体，因此仔细控制这些氧化还原对对于正常的脑功能至关重要。尽管如此，对脑内或星形胶质细胞中NAD+和NADH含量的控制知之甚少。因此，我们在这里分析了小鼠组织和培养的皮质星形胶质细胞的NAD+和NADH含量。从新生小鼠到成年小鼠的发育过程中，大多数组织中的NAD+/NADH比率增加。培养的星形胶质细胞的基础氧化还原比约为3.8，与新生小鼠皮质的氧化还原比相似。虽然这些细胞的NADH含量对能量底物的浓度和能量代谢的调节高度敏感，但NAD+含量在这些条件下令人惊讶地恒定。相比之下，作为NAD+生物合成的前体的烟酰胺或烟酰胺单甘肽的应用缓慢地增加NAD+含量，同时使NADH水平不受影响。最后，抑制NAD+降解酶聚（ADP-核糖）聚合酶略微增加NAD+含量，而不影响NADH水平，而抑制sirtuins没有影响。这些结果表明，除了在氧化还原反应期间将NAD+转化为NADH以及反之亦然之外，该氧化还原对的两个配偶体的含量还受到其他机制的控制。© 2011 Wiley利斯公司
The intracellular redox state is established by several redox pairs, such as NAD+/NADH and NADP+/NADPH and glutathione. This redox state is a crucial determinant of cellular metabolism and function. Astrocytes are an important cell population contributing to brain metabolism and brain energy supply, so a careful control of these redox pairs is essential for proper brain function. Despite this, little is known about control of the NAD+ and NADH content within the brain or in astrocytes. Therefore, we here analyzed the NAD+ and NADH content of mouse tissue and cultured cortical astrocytes. The NAD+/NADH ratio increased in most tissues during development from newborn to adult mice. The basal redox ratio of cultured astrocytes was about 3.8 and similar to the redox ratio of the cortex of newborn mice. Although the NADH content of these cells was highly sensitive to the concentration of energy substrates and to modulation of energy metabolism, the NAD+ content was surprisingly constant under these conditions. In contrast, application of nicotine amide or nicotinamide mononucleotide, which are precursors for NAD+ biosynthesis, slowly increased NAD+ content while leaving NADH levels unaffected. Finally, inhibiting the NAD+‐degrading enzyme poly‐(ADP‐ribose)‐polymerase increased NAD+ content slightly without affecting NADH levels, whereas inhibition of sirtuins had no effect. These results indicate that, in addition to converting NAD+ to NADH and vice versa during redox reactions, the content of both partners of this redox pair is additionally controlled by other mechanisms. © 2011 Wiley‐Liss, Inc.