Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress

Quantification of VGF- and pro-SAAS-derived peptides in endocrine tissues and the brain, and their regulation by diet and cold stress
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DOI:
10.1016/j.brainres.2006.02.124
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发表时间:
2006-05-17
期刊:
影响因子:
2.9
通讯作者:
Salton, Stephen R. J.
Salton, Stephen R. J.
中科院分区:
医学3区
文献类型:
--
作者:
Chakraborty, Tandra R.;Tkalych, Oleg;Salton, Stephen R. J.

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两种新的颗粒蛋白样多肽,VGF和pro-SAAS,它们储存在分泌囊泡中并从分泌囊泡释放,并且在神经、内分泌和神经内分泌组织中广泛表达,在体重、摄食和能量消耗的调节中起作用。VGF和pro-SAAS都被切割成肽片段,其中一些具有生物活性。我们利用了一种高度敏感和特异性的放射免疫测定法(RIA)的免疫反应性,pro-SAAS衍生的PEN肽,开发了另一种针对免疫反应性,VEGF衍生的AQEE 30肽,并定量这些肽在各种小鼠组织和脑区。免疫反应性AQEE 30在垂体中最丰富,而大脑水平在下丘脑、纹状体和额叶皮质中最高。免疫反应性PEN水平在胰腺和脊髓中最高,在脑中,PEN在纹状体、海马、脑桥和髓质以及皮质中最丰富。由于这两种肽在下丘脑中表达,下丘脑是控制进食和能量消耗的大脑区域,因此采用双标记免疫荧光研究。这些结果表明,42%的下丘脑弓状神经元共表达VGF和SAAS肽,并且这些肽在弓状神经元中的细胞内分布不同。通过放射免疫分析,冷应激增加了女性而不是男性下丘脑中的免疫反应性AQEE 30和PEN肽水平,而高脂饮食增加了女性而不是男性海马中的AQEE 30和PEN肽水平。因此,VGF和SAAS衍生肽广泛表达于内分泌、神经内分泌和神经组织中,可通过RIA准确定量,并且在大脑中通过饮食和冷应激进行差异调节。(c)2006 Elsevier B. V.保留所有权利。
Two novel granin-like polypeptides, VGF and pro-SAAS, which are stored in and released from secretory vesicles and are expressed widely in nervous, endocrine, and neuroendocrine tissues, play roles in the regulation of body weight, feeding, and energy expenditure. Both VGF and pro-SAAS are cleaved into peptide fragments, several of which are biologically active. We utilized a highly sensitive and specific radioimmunoassay (RIA) to immunoreactive, pro-SAAS-derived PEN peptides, developed another against immunoreactive, VGF-derived AQEE30 peptides, and quantified these peptides in various mouse tissues and brain regions. Immunoreactive AQEE30 was most abundant in the pituitary, while brain levels were highest in hypothalamus, striatum, and frontal cortex. Immunoreactive PEN levels were highest in the pancreas and spinal cord, and in brain, PEN was most abundant in striatum, hippocampus, pons and medulla, and cortex. Since both peptides were expressed in hypothalamus, a region of the brain that controls feeding and energy expenditure, double label immunofluorescence studies were employed. These demonstrated that 42% of hypothalamic arcuate neurons coexpress VGF and SAAS peptides, and that the intracellular distributions of these peptides in arcuate neurons differed. By RIA, cold stress increased immunoreactive AQEE30 and PEN peptide levels in female but not male hypothalamus, while a high fat diet increased AQEE30 and PEN peptide levels in female but not male hippocampus. VGF and SAAS-derived peptides are therefore widely expressed in endocrine, neuroendocrine, and neural tissues, can be accurately quantified by RIA, and are differentially regulated in the brain by diet and cold stress. (c) 2006 Elsevier B.V. All rights reserved.