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NUCB2/nesfatin-1在中枢和外周的表达及分布

Central and peripheral expression and distribution of NUCB2/nesfatin-1.

作者信息

Goebel-Stengel Miriam, Wang Lixin

机构信息

Department of Internal Medicine, Martin-Luther-Hospital, Caspar-Theyß-Str. 27-31, 14193 Berlin, Germany.

出版信息

Curr Pharm Des. 2013;19(39):6935-40. doi: 10.2174/138161281939131127124814.

DOI:10.2174/138161281939131127124814
PMID:23537079
Abstract

Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2). The antibody against nesfatin-1 recognizes both full length of NUCB2 and nesfatin-1, thus the immunolabeling represents NUCB2/nesfatin-1. It has been found that NUCB2/nesfatin-1 is widely distributed in the rodent central nervous system. The immunoreactivity is more intensive in the brain autonomic centers that regulate feeding, neuroendocrine and cardiovascular functions, such as the hypothalamic paraventricular nucleus, supraoptic nucleus, lateral hypothalamic area, Edinger-Westphal nucleus, locus coeruleus, dorsal vagal complex and medullary raphe nuclei. In neurons, NUCB2/nesfatin-1 is located in the soma and primary dendrites, not in nerve fibers. NUCB2/nesfatin-1 is co-localized with several neurotransmitters involved in regulation of food intake, autonomic and neuroendocrine functions, including oxytocin, vasopressin, neuropeptide Y, cocaine- and amphetamine-regulated transcript, proopiomelanocortin, α-melanocyte-stimulating hormone, melanin-concentrating hormone, leptin, mammalian target of rapamycin, urocortin-1, corticotropin-releasing factor and serotonin. In the periphery, NUCB2/nesfatin-1 is located mainly in the pituitary, gastric mucosa where it coexists with ghrelin, and pancreatic endocrine cells containing insulin. Nesfatin-1 is detectable in the cerebrospinal fluid of rats. NUCB2/nesfatin-1 is measurable in the plasma, and altered under different conditions in rodents and humans, such as immune challenge, high fat diet and exercise, anorexia nervosa, anxiety and depression. Anatomical data suggest that nesfatin-1 is a unique neuroendocrine peptide that may be involved in regulation of homeostasis.

摘要

Nesfatin-1是核结合蛋白-2(NUCB2)的N端片段。抗Nesfatin-1抗体可识别全长NUCB2和Nesfatin-1,因此免疫标记代表NUCB2/Nesfatin-1。研究发现,NUCB2/Nesfatin-1广泛分布于啮齿动物中枢神经系统。在调节进食、神经内分泌和心血管功能的脑自主神经中枢,如下丘脑室旁核、视上核、下丘脑外侧区、动眼神经副核、蓝斑、迷走神经背侧复合体和延髓中缝核,免疫反应性更强。在神经元中,NUCB2/Nesfatin-1位于胞体和初级树突,而非神经纤维。NUCB2/Nesfatin-1与几种参与食物摄入、自主神经和神经内分泌功能调节的神经递质共定位,包括催产素、加压素、神经肽Y、可卡因和苯丙胺调节转录物、阿片促黑素皮质素原、α-黑素细胞刺激素、黑素浓集激素、瘦素、雷帕霉素哺乳动物靶点、尿皮质素-1、促肾上腺皮质激素释放因子和5-羟色胺。在周围组织中,NUCB2/Nesfatin-1主要位于垂体、与胃泌素共存的胃黏膜以及含胰岛素的胰腺内分泌细胞。在大鼠脑脊液中可检测到Nesfatin-1。在血浆中可检测到NUCB2/Nesfatin-1,且在啮齿动物和人类的不同条件下会发生变化,如免疫应激、高脂饮食和运动、神经性厌食症、焦虑和抑郁。解剖学数据表明,Nesfatin-1是一种独特的神经内分泌肽,可能参与内环境稳态的调节。

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