Study on the function and method of 1 and protein sulfhydryl modification.
2. The mechanism of oxidative stress/nitric oxide stress in the occurrence and development of diseases and the regulation and application of natural products/traditional Chinese medicine.
3. Study on the function and molecular mechanism of phosphatidylinositol 4- kinase Ⅱ α (PI4K Ⅱ α) and nitric oxide metabolism regulatory protein S- nitroglutathione reductase (GSNOR).
Major achievements:
The role of nitrosation modification in regulating nuclear transport in protein was revealed, and it was found that nitric oxide regulated the function of nuclear export receptor CRM 1 through nitrosation modification, which expanded the understanding of nuclear export regulation mechanism and biological function of nitric oxide. This paper reveals the mutual regulation of nitrosation-ubiquitination-SUMO modification in protein. This work shows that regulating other post-translational modifications in protein may be an important way for sulfhydryl nitrosation to play its role.
This paper reveals the regulation of NO metabolism on learning and memory, puts forward the viewpoint that NO biological activity is regulated by synthesis and metabolism, and partly reveals the physiological significance of NO metabolic enzyme GSNOR in nervous system.
In order to solve the problem of endogenous nitrosation detection, a quantitative Qualcomm nitrosation detection method was established. Finding and eliminating false positive signals in nitrosation detection has aroused widespread concern in this field. In particular, we established an irreversible avidin labeling method (IBP), which is the only specific nitrosation detection method that can eliminate the interference of intermolecular disulfide bonds and -SSH sulfhydryl modification.
We found new tumor growth regulatory proteins, phosphoinositide 4- kinase Ⅱ α, PI4KIIα. This protein α subtype specifically regulates HER-2/PI3K, ERK 1/2 signal pathways, regulates the synthesis of HIF- 1α protein, and affects the downstream angiogenic factor VEGF of HIF- 1. The expression of iNOS and other proteins affects the ability of endothelial cells to form tubes and migrate, and then affects angiogenesis, and finally regulates the growth of tumors. At present, we have constructed PI4KIIα transgenic mice and are studying the mechanism of PI4KIIα in tumor cell metastasis.
Biography & introduction
Chen Chang, Ph.D., Professor, Institute of Biophysics, Chinese Academy of Sciences
1996, Dr. Peking University
1998, Associate Professor, Institute of Biophysics, Chinese Academy of Sciences;
1998-2000, visiting scientist, British Food Research Institute; 2000-Researcher, Institute of Biophysics, Chinese Academy of Sciences (full professor in 2004).
Professional activities:
Vice President of China Society of Free Radical Biology and Medicine.
Deputy Editor-in-Chief of Journal of Biophysics (Journal of China Biophysics Society).
Member of the Editorial Board of the Open Journal of Nitric Oxide.
Member of Editorial Board of Progress in Biochemistry and Biophysics.
Research interests:
Biological activity of nitric oxide and redox protein sulfhydryl modification: natural product development; Function of phosphatidylinositol 4- kinase iiα(pi 4kiα) and-nitrosoglutathione reductase (GSNOR) in transgenic mice.
Nitric oxide, as a hypothetical messenger, participates in physiological and pathological processes. In addition to the well-known cGMP-dependent NO signaling pathway, there is also a cGMP-independent pathway involving S- nitrosation. S- nitrosation is a ubiquitous nitric oxide that redox modifies cysteine sulfhydryl S, and it transduces the biological activity of NO. The mechanism and cellular effect of this redox-based protein post-translation modification have not been fully understood. The way we understand this process includes three aspects:
1) To study the effects of NO on protein properties, such as folding kinetics, stability, enzyme activity, protein-protein interaction and complex assembly. This division of labor provides a basis for the study of cell effects.
2) We are interested in studying how SNO affects intracellular events, such as protein localization, protein interaction, and how NO and SNO affect the cascade of apoptosis and differentiation. We are also screening natural products with antioxidant/nitrite stressor activity.
3) Study the effects of NO and SNO on the whole organism level, such as memory and diseases (diabetes, cancer, neurodegenerative diseases).
As the chief scientist, Professor Chen has received many research grants, including the National Basic Research Plan (or 973 Plan), the National High-tech Research and Development Plan (863 Plan), the National Natural Science Foundation, the Young Scientists Group Project of China Academy of Sciences, and the Knowledge Innovation Project of China Academy of Sciences.
Some publications (* as communication authors, total =39)
1. Hou Qinglin, Jiang Haiqun, Zhang Xiaoxiang, Guo Chunchun, Huang Bingliang, Wang Bingping, Wang Tingping, Wu Guoyou; Li Jun and Gong Zhenfeng; Du Liangbin, Liu Yanyan, Liu Liling and *. The metabolism of nitric oxide controlled by formaldehyde dehydrogenase (fdh, a homologue of mammalian GSNOR) plays an important role in the visual pattern memory of Drosophila. Nitric oxide: Biology and Chemistry (20 1 1) 24, 17-24.
2. Zhang, Huang, Zhou and Chen. Quantitative analysis of liver S- nitrosoprotein in diabetic mice by ICAT switch method. Protein and nutrition. Cells (20 10) 1(7), 675-87.
3. Huang he. The irreversible biotinylation procedure was used to detect S- nitrosation (IBP) in protein. Free radic. biology Medicine. (20 10) 49, 447–456.
4. X. Zhou, P. Han, J. Li, X. Zhang, B. Huang He *. Protein omics quantification of endogenous S- nitrosation. PLoS ONE(20 10)5(4):e 100 15。 doi: 10. 137 1/journal . pone . 00 100 15。
5. Li Junming, Lv Yan, Zhang Junhong, Kang Hong, Qin Zhenhua and *. PI4KIIα is a new tumor growth regulator, which regulates angiogenesis and HIF- 1α. Oncogene (20 10) 29, 2550-2559.
6. Zhuang Junjie, Jiang Dongxiang, Lu Dalin, Luo Yaoting, Zheng Zhenguo, Feng Junjie, Yang Dalin, Chen Chang and Yan Xiaoyan. Reactive oxygen species induction of CD 146 dimerization in VEGF signal transduction mediated by NADPH oxidase 4. Free radic. biology Medicine. (20 10) 49, 227-236.
7. P. Wang, G.H. Liu, K.Y. Wu, J. Qu, B. Huang, X. Zhang, X. Zhou, L. Gerace and. Inhibition of classical nuclear output by s-nitrosation of CRM1.j.cellsci. (2009) 122, 3772-3779.
8. Duan Shijie, Wan Liqun, Fu Weijun, Pan Hailong, Ding Qing, Han Peiwen, Zhu Xiaoyan, Du Liyuan, Liu Hongxiang, Chen Yaoxiang, Liu Ximing, Yan Xiaodong, Deng Minghong and Qian Ping. Nonlinear synergistic effect of bax expression induced by p53-ING 1 and protein S- nitrosation in apoptosis of thymocytes induced by GSNO: a cross-platform verification quantitative method. Apoptosis (2009) 14(2), 236-45.
9. Han Peiwei, Zhou Xiaoxia, Huang Bingliang, Zhang Xiaoxia and *, Gel fluorescence visualization and site identification of S- nitrosated protein. Anal. Biochemistry. (2008) 377, 150- 155.
10. Han He *. Analysis of S- nitrosated protein by detergent-free biotin switch and LC-MS/MS. Fast communication. Mass spectrometer. (2008) 22(8), 1 137- 1 145.
1 1. Duan Qirui and Zhang zhen. S- nitrosation/anti-nitrosation and apoptosis of immune cells. Cells. Moore. Immunology. (2007) 4 (5), 353-358.
12. Qu Junjie, Liu Guanghan, Wu Guozhen, Han Pengwei, Wang, Li Junming, Zhang Xiaoxiang. Nitric oxide makes Pias3 unstable and regulates sumo. PLoS ONE(2007)2( 10):e 1085。 doi: 10. 137 1/journal . pone . 000 1085。
13. Liu Guanghan, Huang Bingliang and *. Nitric oxide controls the nuclear output of APE 1/Ref- 1 through the S- nitrosation of cysteine 93 and 3 10/. Nucleic acid research (2007) 35, 2522-2532.
14. He Jianping, Wang Chuanping, Han Peiwen and *, A new mechanism of neuronal susceptibility to nitric oxide: the occurrence and regulation of S- nitrosation in protein is the focus of research. Doctor of Neurochemistry. (2007) 102, 1863– 1874.
15. Huang He. An ascorbic acid-dependent artifact that interferes with the analysis and interpretation of biotin switch. Free radic. biology Medicine. (2006) 4 1, 562–567.
16. He Junxiang, Kang Haijun, Yan Fangfeng and Chen Chang *. Endoplasmic reticulum-related events in cerebellar granule cell neurotoxicity induced by S- nitrosoglutathione. brain RES .(2004) 10 15，25-33。
17. Huang Bingliang, Zhang Junsheng, Hou Jingwei and *. The ability of nano-selenium to scavenge free radicals in vitro. Free radic. biology Medicine. (2003) 35(7), 805-8 13.
18. Wei, Hou, Xin and Sheng Akita. Nitric oxide induces oxidative stress and apoptosis in neurons. Journal of biochemistry and biophysics. Cell Research (2000) 1498, 72-79.
19., H. R. Tang, L. Sutcliffe and P. Belton, green tea polyphenols scavenging 1, 1- diphenyl -2- picryl-hydrazine radical in liposome bilayer-direct evidence from ESR study. Agrich. Food chemistry. (2000) 8, 57 10-57 14.
20. Wei Tianwei, Chin Hung Kao, Zhao Benliang, Hou Junwei, Xu Haihong, Xin Weijun and Parker. Different effects of EGb76 1 on apoptosis of rat cerebellar granule cells induced by hydroxyl radicals. Moore. biology (IUBMB Life Insurance) (1999) 47,397-405.
National invention patents:
1. A method for specifically detecting sulfhydryl modification of protein or polypeptide, the application number of which is 2009 10084 155.7.
2. Application of phosphoinositide 4- kinase type 2 α subtype PI4KIIα with application number of 200810/04272.0.