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首页> 外文期刊>Frontiers in neuroendocrinology >VGF: a novel role for this neuronal and neuroendocrine polypeptide in the regulation of energy balance.
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VGF: a novel role for this neuronal and neuroendocrine polypeptide in the regulation of energy balance.

机译：VGF：这种神经元和神经内分泌多肽在调节能量平衡中的新作用。

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摘要

Insight into the mechanisms of action of neurotrophic growth factors has been obtained through the identification and characterization of gene products that are regulated or modified at the transcriptional, translational, and/or posttranslational level in response to neurotrophin treatment. VGF (non-acronymic) was identified approximately 15 years ago as a nerve growth factor (NGF)-regulated transcript in rat PC12 pheochromocytoma cells. Subsequent studies have demonstrated that neurotrophins such as NGF and brain-derived neurotrophic factor induce vgf gene expression relatively rapidly in PC12 cells and cultured cortical neurons, respectively, in comparison to less robust regulation by epidermal growth factor (EGF) and insulin, growth factors which do not trigger the neuronal differentiation of PC12 cells. vgf gene expression is stimulated in vitro by NGF and the ras/map kinase signaling cascade through a CREB-dependent mechanism, while in vivo, VGF mRNA levels are regulated by neuronal activity, including long-term potentiation, seizure, and injury. Both the mRNA and encoded approximately 68-kDa protein (VGF) are selectively synthesized in neuroendocrine and neuronal cells. The predicted VGF sequence is rich in paired basic amino acid residues that are potential sites for proteolytic processing, and VGF undergoes regulated release from dense core secretory vesicles. Although VGF mRNA is synthesized widely, by neurons in the brain, spinal cord, and peripheral nervous system, its expression is particularly abundant in the hypothalamus. In addition, VGF peptides are found in hypophysial, adrenal medullary, gastrointestinal, and pancreatic endocrine cells, suggesting important neuroendocrine functions. Recent analysis of VGF knockout mice indeed demonstrates that VGF plays a critical role in the control of energy homeostasis. VGF knockout mice are thin, small, hypermetabolic, hyperactive, and relatively infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic pro-opiomelanocortin, neuropeptide Y, and agouti-related peptide expression. Coupled with the demonstration that VGF mRNA levels are induced in the normal mouse hypothalamic arcuate nuclei in response to fasting, important central and peripheral roles for VGF in the regulation of metabolism are suggested. Here we review previous studies of VGF in the broader context of its newly recognized role in the control of energy balance and propose several models and experimental approaches that may better define the mechanisms of action of VGF. Copyright 2000 Academic Press.
机译：通过鉴定和表征响应神经营养蛋白治疗而在转录，翻译和/或翻译后水平上调节或修饰的基因产物，已经获得了对神经营养生长因子作用机制的深入了解。 VGF（非急性）是在大鼠PC12嗜铬细胞瘤细胞中被神经生长因子（NGF）调节的转录物。随后的研究表明，与表皮生长因子（EGF）和胰岛素（生长因子）相比，NGF和脑源性神经营养因子等神经营养因子分别在PC12细胞和培养的皮质神经元中分别较快地诱导vgf基因表达。不会触发PC12细胞的神经元分化。 NGF和ras / map激酶信号传导通过CREB依赖性机制在体外刺激vgf基因表达，而在体内，VGF mRNA水平受神经元活性（包括长期增强，癫痫发作和损伤）的调节。在神经内分泌和神经元细胞中选择性合成了mRNA和约68 kDa的编码蛋白（VGF）。预测的VGF序列富含成对的碱性氨基酸残基，这些残基是蛋白水解过程的潜在位点，并且VGF经历从致密核心分泌囊泡的调节释放。尽管VGF mRNA由脑，脊髓和周围神经系统中的神经元广泛合成，但其表达在下丘脑中尤其丰富。此外，VGF肽存在于垂体，肾上腺髓质，胃肠道和胰腺内分泌细胞中，提示重要的神经内分泌功能。对VGF基因敲除小鼠的最新分析确实表明，VGF在控制能量稳态中起着至关重要的作用。 VGF基因敲除小鼠是瘦，小，代谢亢进，活动过度和相对不育的，具有显着降低的瘦素水平和脂肪储存，并改变了下丘脑前视紫红质皮质激素，神经肽Y和与刺豚鼠有关的肽表达。结合证明禁食可在正常小鼠下丘脑弓状核中诱导VGF mRNA水平的现象，提出了VGF在代谢调节中的重要中枢和外周作用。在这里，我们回顾了VGF在能量平衡控制中新近认可的作用的更广泛背景下的先前研究，并提出了一些模型和实验方法，可以更好地定义VGF的作用机理。版权所有2000学术出版社。

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