Interactions of peptide amidation and copper: Novel biomarkers and mechanisms of neural dysfunction
Interactions of peptide amidation and copper: Novel biomarkers and mechanisms of neural dysfunction
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DOI：
10.1016/j.nbd.2009.09.016
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发表时间：
2010-01-01
影响因子：
6.1
通讯作者：
Eipper, Betty A.
中科院分区：
文献类型：
--
作者：
Bousquet-Moore, Danielle;Prohaska, Joseph R.;Eipper, Betty A.
哺乳动物基因组仅编码少量的铜酶。许多基因参与协调铜的吸收、分布、储存和流出，使得基因/营养相互作用对这些铜酶特别重要。铜缺乏和铜过量都会破坏神经功能。使用肽酰甘氨酸α-酰化单加氧酶（PAM）杂合子小鼠，PAM是合成许多神经肽所必需的铜酶。我们确定了焦虑样行为、体温调节和癫痫敏感性的改变。膳食铜补充剂逆转了这些缺陷的一个子集。维持轻微铜缺乏饮食的野生型小鼠表现出在PAM（+/-）小鼠中观察到的一些相同缺陷，并且表现出PAM代谢的改变。PAM（+/-）小鼠中铜稳态的改变表明PAM在铜代谢的细胞类型特异性调节中的作用。对PAM的遗传限制敏感的生理功能可被补充铜逆转，并被铜缺乏模仿，这可能是边缘铜缺乏的指标。(C)2009 Elsevier Inc. All rights reserved.
Mammalian genomes encode only a small number of cuproenzymes. The many genes involved in coordinating copper uptake, distribution, storage and efflux make gene/nutrient interactions especially important for these cuproenzymes Copper deficiency and copper excess both disrupt neural function. Using mice heterozygous for peptidylglycine alpha-armdating monooxygenase (PAM), a cuproenzyme essential for the synthesis of many neuropeptides. we identified alterations in anxiety-like behavior, thermoregulation and seizure sensitivity. Dietary copper supplementation reversed a subset of these deficits. Wildtype mice maintained on a marginally copper-deficient diet exhibited some of the same deficits observed in PAM(+/-) mice and displayed alterations in PAM metabolism. Altered copper homeostasis in PAM(+/-) mice suggested a role for PAM in the cell type specific regulation of copper metabolism Physiological functions sensitive to genetic limitations of PAM that are reversed by supplemental copper and mimicked by copper deficiency may serve as indicators of marginal copper deficiency. (C) 2009 Elsevier Inc. All rights reserved.