D-天冬氨酸调节黑皮质素的形成和功能：D-天冬氨酸氧化酶缺陷小鼠的行为改变。
D-aspartate regulates melanocortin formation and function: behavioral alterations in D-aspartate oxidase-deficient mice.
作者信息
Huang Alex S, Beigneux Anne, Weil Zachary M, Kim Paul M, Molliver Mark E, Blackshaw Seth, Nelson Randy J, Young Stephen G, Snyder Solomon H
机构信息
Department of Neuroscience, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
出版信息
J Neurosci. 2006 Mar 8;26(10):2814-9. doi: 10.1523/JNEUROSCI.5060-05.2006.
D-aspartate, an abundant D-amino acid enriched in neuroendocrine tissues, can be degraded by D-aspartate oxidase (Ddo). To elucidate the function of D-aspartate, we generated mice with targeted deletion of Ddo (Ddo(-/-)) and observe massive but selective augmentations of D-aspartate in various tissues. The pituitary intermediate lobe, normally devoid of D-aspartate from endogenous Ddo expression, manifests pronounced increases of immunoreactive D-aspartate in Ddo(-/-) mice. Ddo(-/-) mice show markedly diminished synthesis and levels of pituitary proopiomelanocortin/alpha-MSH, associated with decreased melanocortin-dependent behaviors. Therefore, Ddo is the endogenous enzyme that degrades D-aspartate, and Ddo-enriched organs, low in D-aspartate, may represent areas of high turnover where D-aspartate may be physiologically important.
D-天冬氨酸是一种在神经内分泌组织中大量富集的D-氨基酸，可被D-天冬氨酸氧化酶（Ddo）降解。为了阐明D-天冬氨酸的功能，我们构建了Ddo基因靶向缺失的小鼠（Ddo(-/-)），并观察到各种组织中D-天冬氨酸大量但选择性地增加。垂体中间叶通常因内源性Ddo表达而不含D-天冬氨酸，但在Ddo(-/-)小鼠中，免疫反应性D-天冬氨酸显著增加。Ddo(-/-)小鼠的垂体促肾上腺皮质激素原/α-促黑素细胞激素的合成和水平明显降低，这与黑素皮质素依赖性行为减少有关。因此，Ddo是降解D-天冬氨酸的内源性酶，而富含Ddo、D-天冬氨酸含量低的器官可能代表了D-天冬氨酸生理上可能很重要的高周转率区域。
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