Leptin fragments induce Fos immunoreactivity in rat hypothalamus
Leptin fragments induce Fos immunoreactivity in rat hypothalamus
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DOI：
10.1016/j.regpep.2004.11.001
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发表时间：
2005-04-15
影响因子：
--
通讯作者：
Miranda, A
中科院分区：
文献类型：
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作者：
Oliveira, VX;Fázio, MA;Miranda, A
瘦素在哺乳动物的能量平衡和神经内分泌控制中起重要作用。在试图确定区域的瘦素分子负责其生物活性，我们已经合成了六个肽的蛋白质的三维结构的基础上。通过固相法合成片段，通过反相高效液相色谱法（RP-HPLC）纯化，并通过液相色谱-电喷雾电离质谱法（LC/ESI-MS）表征。将它们静脉注射，并将它们诱导大鼠下丘脑Fos免疫反应性（Fos-ir）的能力与重组人瘦素和生理盐水进行比较。Ac-[Ser（117）]Lep（116-140）-NH_2（V）片段在表达瘦素受体长型的下丘脑核团中诱导Fos免疫反应。其他五个片段没有观察到类似的能力。为了研究Fos-ir是否在瘦素激活的同一神经元组中诱导，我们进行了可卡因和安非他明调节转录本（CART）的双标记免疫组化，这是一种与瘦素在大鼠下丘脑中的作用相关的神经肽。我们发现Ac-[Ser（117）]Lep（116-140）-NH 2（V）通过弓状核的吻尾侧延伸差异激活CART神经元。这些结果表明，该片段在同一组神经元中起作用，介导瘦素反应。该方法为开发瘦素相关化合物提供了基础，具有潜在的应用前景。(C)2004年由Elsevier B. V.出版
Leptin presents an important role in energy balance and neuroendocrine control in mammals. In an attempt to identify regions of the leptin molecule responsible for its bioactivity, we have synthesized six peptides based on the protein three-dimensional structure. Fragments were synthesized by the solid-phase methodology, purified by reverse-phase high-performance liquid chromatography (RP-HPLC), and characterized by liquid chromatography-electrospray ionization mass spectrometry (LC/ESI-MS). They were injected intravenously and their ability to induce Fos immunoreactivity (Fos-ir) in rat hypothalamus was compared with that of the recombinant human leptin and saline. Fragment Ac-[Ser(117)]Lep(116-140)-NH2 (V) induced Fos-ir in hypothalamic nuclei that express leptin receptor long form. No similar ability was observed for the other five fragments. To investigate whether Fos-ir was induced in the same neuronal group activated by leptin, we proceeded with a dual-label immunohistochemistry for cocaine- and amphetamine-regulated transcript (CART), a neuropeptide related to leptin action in rat hypothalamus. We found that Ac-[Ser(117)]Lep(116-140)-NH2 (V) differentially activates CART neurons through the rostrocaudal extension of the arcuate nucleus. These results suggest that this fragment acts in the same group of neurons that mediate leptin response. This approach may offer the basis for the development of leptin-related compounds, having potential application in human or veterinary medicine. (C) 2004 Published by Elsevier B.V.