本实验室主要兴趣在于：
神经生长抑制因子(GIF)是是神经系统中第一个被鉴定具有神经元生长抑制功能的蛋白质。1991年，Uchida等在研究阿尔茨海默病(Alzheimer’s Disease, AD)时从人脑组织中首次分离得到该物质。GIF特异分布于中枢神经系统，且其基因及蛋白结构与MT高度同源，属于金属硫蛋白(metallothionein, MT) 第三亚型I(MT-III)，GIF的下调被认为与AD的发生有着密切的关系。MT分子均由?-,?-结构域及一个保守的连接区组成。GIF 的?-结构域为其功能结构域，而β-结构域的CPCP区为其可能的生物学功能位点。然而， GIF是如何表现其生物学功能的？GIF与AD的关系又如何呢？这些问题都亟待进一步的研究。
金属硫蛋白（Metallohinein, MT）是一类低分子量、富含半胱氨酸的金属结合蛋白,其参与体内必需金属元素的代谢、有毒重金属解毒以及细胞应激等。MT表达最显著的特征是能被重金属离子、细胞因子、应激条件以及甾族激素等多种物质和条件诱导。水生动物体内的MT含量常作为评价水体重金属污染的生物标识物，因此对于鱼类MT含量测定及基因转录调控机制的研究将为MT在金属污染的生物监测的应用提供了理论依据。我们建立了白鲫鱼MT的纯化鉴定的方法，并证明白鲫鱼MT基因上游调控区域存在多种转录调节元件，如金属反应元件(MRE)、糖皮质激素反应元件(GRE)和抗氧化元件（ARE)等，分析其功能。
Research Description:
Neuronal growth inhibitory factor (GIF) was the first demonstrated as a neuronal growth inhibitor. It’s first isolated by Uchida (1991) from human brain while he studied in Alzheimer’s disease (AD). Based on its highly gene homologous characterization of the function and protein structure with Metallothionein(MT), GIF was named as brain-specific member of the metallothionein (MT) family, MT-III. GIF was drastically reduced at both protein and mRNA levels and down-regulated in AD brains were suggested to be closely related to the etiology of AD pathological process. GIF consists of ?, ?-domain and a constant linker. The GIF?-domain was proved to be the functional domain and CPCP region was considered to play a critical role in its biological activity. However, How can the ?-domain and the CPCP region be functional in GIF and how is GIF implicated to function in AD pathological process are need to be answered by study on.
Metallothioneins are a family of low molecular weight, cysteine-rich, metal-binding proteins, which play important roles in metal ion homeostasis, detoxification, and cytoprotection during the acute phase response. The most conspicuous feature of MT is its inducibility by a variety of agents and conditions, including heavy metal ions, cytokines, stress, and hormones. The MT quantitation as an indicator in aquatic creature and the analyzing of the genes promoter region can validate to value the pollution of waters. We set up the routine methods of purifying and determining MTs in crucian carp (Carassius cuvieri), demonstrated the exist of various cis-acting elements in the promoter region of MT gene, such as metal regulatory element (MRE), glucocorticoid responsive element (GRE), or antioxidant response element (ARE) etc, then analyzing them.
代表性论文
1. Da Huang, Jianrong Zhang, Yongchao Fu, Liming Lu, Yiming Xu , Lingyan Ma, Minxiang Li, Lingyuan Xiong1 , Hongwei Ren* , Quantitative Determination for Nerve Growth Factor Concentration in Commercial Product by SEC‐HPLC , Bioscience Methods , 2011 , 2: 1-5
2. Zhiguo Sun, Hongwei Ren(co-Firt Author) ,Yan Liu, Jessica L. Teeling and Jun Gu , Phosphorylation of RIG-I by casein kinase II inhibits its anti-viral response , J. Virology , 2011 , 85:1036-47
3. Feng Liu, Su Wu, Hongwei Ren , Jun Gu* , Klotho suppresses RIG-I mediated senescence-associated inflammation , Nature Cell Biology , 2011 , 13: 254-62
4. Xu L, Xiao N, Liu F, Ren HW and Gu J , Inhibition of RIG-I and MDA5-dependent antiviral response by gC1qR at mitochondria , Proc Natl Acad Sci USA , 2009 , 106(5):1530-1535
5. Pengfei He, Mingxu Xu, Hongwei Ren* , Cloning and functional characterization of 5'-upstream region of metallothionein-I gene from Crucian Carp (Carassius cuvieri) , International Journal Biochemistry & Cell Biology , 2007 , 39(4):832-41
6. Binyun Ma, Hongwei Ren*, Jianping Wu et al , Molecular Cloning of cDNA Endoding for MT-I/MT-II and Analyzing of the Protein Structure in Yark , China Biotechnology , 2007 , 25, 62~68
7. Hongwei Ren*, Mingxu Xu, Pengfei He et al, , Cloning of crucian carp (Carassius cuvieri) metallothionein-II gene and characterization of its gene promoter region , Biochemical Biophysical Research Communications , 2006 , 342, 1297-1304
8. Mingming Chu, Zhen-quan Guo, Hong-wei Ren* , Development of ELISA for metallothionein-II allows determination of heavy metal pollution of fresh water , Frontiers in Bioscience , 2006 , 11, 2113-2122
9. Liu Y.,Hongwei Ren., Ji QZ. & Ru BG , Attenuation of zinc-induced neuronal death by the interaction of growth inhibitory factor with Rab3a in rat hippocampal neurons , Neurosci Lett , 2004 , 358, 149-52
10. Hongwei Ren, Binggen Ru, et al. , Different Protective roles in vitro of α- and β-domain of Growth Inhibitory Factor (GIF) on Neuron Injuries Caused by Oxygen Free Radicals , Biochim. Biophy. Acta , 2001 , 1568, 129~134
11. Hongwei Ren, Ru Binggen , Application of Metallothionein (MT) Genes in Transgenic Aspect , Progress in Bioengineering , 2000 , 4(1); 34-39 |
