VGF及其衍生肽

神经肽VGF广泛存在于中枢神经系统和外周神经系统中,在垂体、肾上腺髓质、胃肠内分泌细胞和胰岛B细胞中亦有表达。神经细胞／内分泌细胞表达VGF多肽受到神经营养因子、神经元活性等因素的调控。目前证实,VGF及其衍生肽参与生物体的能量平衡、新陈代谢以及生殖发育等的凋节。在神经系统变性病及情感性精神障碍的相关研究也日益受到关注。本文就神经肽VGF及其衍生肽的生化、生理特性及病理生理作用做一综述。     

食欲肽及其受体

以前认为在下丘脑的腹内侧区及下丘脑外侧区分别存在饱中枢（ｓａｔｉｅｔｙｃｅｎｔｅｒ）及摄食中枢（ｆｅｅｄｉｎｇｃｅｎｔｅｒ）,进行机体能量平衡的中枢性调节。但随着许多参与机体能量平衡调节的神经递质及神经肽的发现,说明机体能量平衡的中枢性调节并非如此简...     

抗菌肽牛乳铁蛋白肽衍生肽在毕赤酵母中的表达及活性鉴定

利用巴斯德毕赤酵母系统表达抗菌肽牛乳铁蛋白肽衍生肽简称LfcinBD,获得的表达产物具有较强的抗菌活性.将人工设计的用化学合成法合成的以酵母偏爱密码子编码的LfcinBD基因片段克隆到巴斯德毕赤酵母分泌型表达载体pPIC9K中,获得的重组质粒pPIC9K-LfcinBD通过限制性内切酶Sac Ⅰ酶切线性化,电击法转化毕赤酵母GS115宿主菌,G418抗性筛选,得到高拷贝转化子.经PCR检测,LfcinBD基因与毕赤酵母染色体稳定整合.阳性克隆经甲醇诱导表达LfcinBD,诱导表达5 d,每24 h取上清1 mL,进行抑菌试验.结果表明,抗菌肽牛乳铁多肽衍生肽基因已整合到酵母细胞基因组中并获得表达,经0.5%甲醇在30℃诱导48 h可产生较强抗菌活性的抗菌肽,而且对氨苄青霉素抗性的大肠杆菌亦有较强的抑菌作用.     

线粒体衍生肽MOTS-c生物学特性及病理生理功能

MOTS-c是一种新的线粒体衍生肽(mitochondrial-derived peptides, MDPs),能调节体内稳态,对机体有保护作用,可以靶向作用于骨骼肌、心肌、血清、脂肪等组织。MOTS-c直接连接线粒体与运动诱导的AMPK通路、TGF-β/Smad通路、AKT通路等信号通路,调控胰岛素敏感性和炎症反应,促进细胞内环境的稳定,从而改善衰老、肥胖、炎症、心血管等慢性疾病。本文探讨了MOTS-c的生物学特性以及其在运动健康促进中的作用。     

机体内环境理化因素对降钙素基因相关肽（CGRP）释放的影响

我们以前的工作表明在内毒素和失血性休克时ＣＧＲＰ释放入血循环。本实验在离体大鼠肠系膜动脉床灌流的模型上,发现低ｐＨ、高乳酸、高氯化钠和高蔗糖溶液均能直接引起ＣＧＲＰ释放增加,进一步应用辣椒素预灌流,ＣＧＲＰ释放的作用被抑制,同时ＣＧＲＰ释放可以被一种钙引起的细胞内钙池释放阻断剂钌红所抑制,而且应用无钙的低ｐＨ,高乳酸及高渗液就不能引起ＣＧＲＰ释放增多,实验结果提示：上述理化因子导致ＣＧＲＰ从大鼠肠     

甲胎蛋白衍生肽作为抗原表位在肝癌免疫治疗中的作用

甲胎蛋白(AFP)作为一种肝癌诊断的标志物,一直受到人们的广泛关注。通过对AFP衍生肽的研究,已经发现AFP衍生肽作为抗原表位在肝癌的生长和发展过程中对T细胞有刺激作用。我们通过阐述AFP衍生肽抗原表位的分布及其对肝细胞癌中T细胞活动的影响,进一步说明AFP衍生肽作为抗原表位在肝癌免疫治疗中的作用。     

神经激肽B及其生殖内分泌作用

神经激肽B(neurokinkin B,NKB)是速激肽家族的一员,主要通过其受体NK3R发挥作用。NKB及NK3R在神经系统分布广泛。NKB具有使空腔脏器平滑肌收缩、松弛血管、降低平均动脉压、减慢心率、兴奋离体大鼠脊髓神经元及收缩瞳孔括约肌缩小瞳孔等生物学作用。近年来NKB在生殖内分泌中的调控作用越来越受到关注,关于其调节下丘脑-垂体-性腺轴(HPGA)的作用的研究也越来越深入。本文综述了NKB及其受体的分布范围、生理功能、NKB在生殖内分泌调控过程中的作用,其具体的作用机制还有待于进一步研究。     

豚鼠胸腺含P物质、降钙素基因相关肽和神经肽Y神经的定位研究

为研究神经肽调节胸腺生理功能的作用途径,作者采用免疫组织化学ＡＢＣ法结合ＧＤＮ增强技术,以３０μｍ厚恒冷箱切片光镜下观察了豚鼠胸腺内含ＳＰ、ＣＧＲＰ和ＮＰＹ神经纤维的定位与分布。结果发现,ＳＰ和ＣＧＲＰ免疫反应神经纤维在胸腺内分布广泛,呈线状或串珠状,可见于血管周围,小叶间结缔组织和胸腺实质。实质中以皮髓质交界区和髓质区纤维分布较密集,而走行于皮质淋巴组织的神经纤维相对稀疏,胸腺小体附近亦可见含ＣＧＲＰ神经分布。含ＮＰＹ神经纤维主要分布于血管周围、小叶间隔和皮髓质交界区,仅少数分支穿行于皮质胸腺细胞之间。胸腺被膜中有上述３种肽能神经纤维分布。本研究结果表明,胸腺内有丰富的肽能神经分布,这可能是神经肽调节胸腺生理功能的重要方式之一。     

Alarin——新的血管活性肽

Alarin是2006年被发现的神经肽galanin家族的新成员。Galanin是1983年Tatemoto K等发现的由23个氨基酸残基组成的肽类物质。1999年Ohtaki T等发现了能够与galanin受体相结合的另一个内源性肽类物质———GALP(galain-like peptide)。GALP由60个氨基酸残基组成,其9~21位氨基酸残     

Tissue-Specific Processing of the Neuroendocrine Protein VGF

Abstract: VGF is a neuroendocrine-specific gene product that is up-regulated by nerve growth factor in the PC12 cell line. In rat neuroendocrine tissues two polypeptides of 90 and 80 kDa were detected by an antiserum to an N-terminal domain of VGF (from residues 4 to 240). In parallel, an antiserum directed against the C-terminal nonapeptide of VGF (from residues 609 to 617) revealed several additional posttranslational products. Peptides of apparent molecular sizes of 20, 18, and 10 kDa were prominent in nerve tissues and the hypophysis but absent in the adrenal medulla, and their relative abundance varied in distinct regions of the CNS. In PC12 cells VGF was proteolytically processed only after nerve growth factor treatment, and primary cultures of rat cerebellar granule cells accumulated the low-molecular-weight forms of VGF during in vitro maturation. In these cells the specific cleavages of VGF occurred in a postendoplasmic reticulum compartment; the processed forms were enriched in the secretory vesicles and were preferentially secreted upon cell membrane depolarization. Distinct differential distribution in the CNS and in vitro release of such posttranslational products indicate that these species may represent biologically relevant forms of VGF that play a role in neuronal communication.     

Isolation and characterization of VGF peptides in rat brain. Role of PC1/3 and PC2 in the maturation of VGF precursor

The neurotrophin responsive gene vgf is widely expressed in central and peripheral neurones, and in certain neuroendocrine cell populations. Its encoded VGF precursor protein (proVGF1: 617 amino acids in rat, 615 in man, > 85% homology) gives rise to several low molecular weight species. We studied a range of neuroendocrine and neuronal cells, in which VGF-processing products were prominent with an apparent molecular weight of 20 and 10 kDa (VGF20 and VGF10, respectively). Such peptides were recognized by antibodies specific for the C-terminal rat VGF nonapeptide, thus indicating that they included the C-terminus of proVGF. Ectopic expression of the neuroendocrine-specific prohormone convertases PC1/3 or PC2 in GH3 cells showed that both could generate VGF20, while VGF10 was preferentially produced by PC1/3. Site-directed mutagenesis was used to identify the KRKRKK(488) motif as the target within VGF sequence which leads to the production of VGF20. Molecular characterization of rat VGF10, on the other hand, revealed that this peptide is produced by cleavage at the RPR(555) site. By the combined use of high-resolution separation techniques, matrix-assisted laser desorption/ionization time of flight (MALDI-ToF) mass spectrometry and manual Edman degradation we identified in rat brain a VGF fragment analogous to bovine peptide V and two novel peptides also derived from the C-terminal region of proVGF.     

Nucleotide Sequence and Regulatory Studies of VGF, a Nervous System-Specific mRNA That Is Rapidly and Relatively Selectively Induced by Nerve Growth Factor

A nervous system-specific mRNA that is rapidly induced in PC12 cells to a greater extent by nerve growth factor (NGF) than by epidermal growth factor treatment has been cloned. The polypeptide deduced from the nucleic acid sequence of the NGF33.1 cDNA clone contains regions of amino acid sequence identity with that predicted by the cDNA clone VGF, and further analysis suggests that both NGF33.1 and VGF cDNA clones very likely correspond to the same mRNA (VGF). In this report both the nucleic acid sequence that corresponds to VGF mRNA and the polypeptide predicted by the NGF33.1 cDNA clone are presented. Genomic Southern analysis and database comparison did not detect additional sequences with high homology to the VGF gene. Induction of VGF mRNA by depolarization and phorbol 12-myristate 13-acetate treatment was greater than by serum stimulation or protein kinase A pathway activation. These studies suggest that VGF mRNA is induced to the greatest extent by NGF treatment and that VGF is one of the most rapidly regulated neuronal mRNAs identified in PC12 cells.     

牛乳酪蛋白源抗菌肽的研究进展

抗菌肽是具有抗菌活性的肽类物质的总称。除了广泛存在于生物体内的内源性抗菌肽外,已从酪蛋白的酶解产物中获得了多种外源性抗菌肽。抗菌肽的抗菌机理独特,有望成为新一代抗菌剂。简要综述了牛乳酪蛋白源抗菌肽的种类、抗菌机理及其研究展望。     

Synthesis and evaluation of N-(4-benzylphenyl)piperazines as VGF inducers

A series of compounds was discovered that induce the production of VGF mRNA in SH-SY5Y cells and exhibit cytoprotection under tunicamycin induced endoplasmic reticulum (ER) stress. The aminophenol ring and linker chain of the template SUN N8075 (1) was modified to yield compounds with higher efficacy and lower propensity for adverse effects.     

大豆蛋白源性肽调节糖脂代谢机制研究进展

大豆蛋白源性肽是大豆蛋白质经酸法或酶法水解后分离精制而得到的多肽混合物,是植物蛋白源性肽的重要来源,大豆蛋白源性肽通过抑制肠道胆固醇吸收、与胆固醇的相互作用、调节胆固醇代谢相关基因（用于降低胆固醇）、甘油三酯代谢相关基因、二肽基肽酶Ⅳ和葡萄糖代谢相关基因,在降低胆固醇、降低甘油三酯、抗肥胖、抑制脂肪酸合成酶和抗糖尿病等代谢调节方面具有重要作用。综述了大豆蛋白源性肽在体内外改善脂质和糖代谢方面的生理功能,并对大豆蛋白源性肽的前景进行了展望,以期为大豆蛋白源性肽的研究与应用提供参考。