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Parkin Somatic Mutations Link Melanoma and Parkinson's Disease

Journal of Genetics and Genomics 2016年第6期43卷 369-379页

作者： Lotan Levin Shani Srour Jared Gartner Oxana Kapitansky Nouar Qutob Shani Dror Tamar Golan Roy Dayan Ronen Brener Tamar Ziv Mehdi Khaled Ora Schueler-Furman Yardena Samuels Carmit Levy department of Human Genetics and biochemistry Sackler Faculty of MedicineTel Aviv University Surgery Branch National Cancer InstituteNIH department of Molecular Cell Biology Weizmann Institute of Science Oncology Institute Edith Wolfson Medical Center Technion Smoler Proteomics center Faculty of BiologyTechnion e Israel Institute of Technology Institut Gustave Roussy INSERM department of Microbiology and Molecular Genetics Institute for Medical Research Israel-CanadaFaculty of MedicineHebrew University

Epidemiological studies suggest a direct link between melanoma and Parkinson＇s disease（PD）; however, the underlying molecular basis is unknown. Since mutations in Parkin are the major driver of early-onset PD and Parkin was recently reported to play a role in cancer development, we hypothesized that Parkin links melanoma and PD. By analyzing whole exome/genome sequencing of Parkin from 246 melanoma patients, we identified five non-synonymous mutations, three synonymous mutations, and one splice region variant in Parkin in3.6% of the samples. In vitro analysis showed that wild-type Parkin plays a tumor suppressive role in melanoma development resulting in cell-cycle arrest, reduction of metabolic activity, and apoptosis. Using a mass spectrometry-based analysis, we identified potential Parkin substrates in melanoma and generated a functional protein association network. The activity of mutated Parkin was assessed by protein structure modeling and examination of Parkin E3 ligase activity. The Parkin-E28 K mutation impairs Parkin ubiquitination activity and abolishes its tumor suppressive effect. Taken together, our analysis of genomic sequence and in vitro data indicate that Parkin is a potential link between melanoma and Parkinson＇s disease. Our findings suggest new approaches for early diagnosis and treatment against both diseases.

关键词： Melanoma Parkinson's disease Parkin Mutation

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心肌缺血再灌注后蛋白质的硝基化及缺血预处理的影响

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生物物理学报 2009年第S1期25卷 396-397页

作者：刘斌 Arun K.Tewari Liwen Zhang Kari B.Green-Church Jay L.Zweier Yeong-Renn Chen Guanglong He 汕头大学医学院心血管研究中心 center for biomedical EPR Spectroscopy and Imaging Davis Heart and Lung Research Instituteand Division of Cardiovascular MedicineDepartment of Internal MedicineCollege of Medicinethe Ohio State UniversityColumbusOH43210USA Campus Chemical Instrument center/mass spectrometry and Proteomics Facility the Ohio State UniversityColumbusOH43210USA

心肌缺血后再灌注时会爆发式地产生大量的一氧化氮(NO)和超氧阴离子自由基(O2?-),二者可以极快的速度反应生成过氧亚硝基阴离子(ONOO-)。

关键词：缺血再灌注活性氧/活性氮蛋白质硝基化缺血预处理

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The ultra-sonication of minerals in swine feed

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Journal of Animal Science and Biotechnology 2015年第4期6卷 416-423页

作者： Mayra A.D.Saleh Pedro M.Padilha Lucelia Hauptli Dirlei A.Berto department of Animal Production Lageado FarmFaculty of Animal Science and Veterinary MedicineUNESP-Sao Paulo State UniversityBotucatu Campus department of Chemistry and biochemistry Institute of BiosciencesUNESP-Sao Paulo State UniversityBotucatu CampusRubiao Junior District UFSC-Federal University of Santa Catarina Center for Agricultural Sciences

A sample preparation method based on ultrasound assisted-extraction （UAE） of Ca, Mg and P from swine feed has been described. The experiment was performed to cover the variables influencing the sonication process and, the method validation using standard reference material. Final solutions obtained upon sonication were analyzed by flame atomic absorption spectrometry （for Ca and Mg） and by UV-vis spectrophotometry （for P）. The best conditions for metal extraction were as follows： sample mass： 100 mg in 20 mL 0.10 mol/L HCI, a particle size：〈60 lam, sonication time： 5 cycles of 10 s and ultrasound power： 102 W. The UAE method was applied in digestibility assays in different piglet feeds and their results showed that it is highly comparable （P 〉 0.05） to the other methods used for such purposes, as block digestion, and offered a Ca, Mg and P method of quantification limit of 10.6, 12.4 and 14 mg/kg, respectively. The major advantages of the UAE method compared to other methods are the high treatment rate, low reagent usage in the extracts and, it does not generate toxic residues that might negatively affect human health and the environment, accompanied by good precision and accuracy.

关键词： Digestibility assay Green analytical chemistry Macronutrients Piglet Ultrasound-assisted extraction

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JARID2 coordinates with the NuRD complex to facilitate breast tumorigenesis through response to adipocyte-derived leptin

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Cancer Communications 2023年第10期43卷 1117-1142页

作者： Wei Liu Yi Zeng Xinhui Hao Xin Wang Jiaxiang Liu Tianyang Gao Mengdi Wang Jingyao Zhang Miaomiao Huo Ting Hu Tianyu Ma Die Zhang Xu Teng Hefen Yu Min Zhang Baowen Yuan Wei Huang Yunkai Yang Yan Wang Key Laboratory of Immune Microenvironment and Disease (Ministry of Education) Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjinP.R.China Key Laboratory of Cancer and Microbiome State Key Laboratory of Molecular OncologyNational Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China department of biochemistry and Molecular Biology School of Basic Medical ScienceSouthwest Medical UniversityLuzhouSichuanP.R.China department of Breast Surgical Oncology National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingP.R.China Beijing Key Laboratory of Cancer Invasion and Metastasis Research Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCapital Medical UniversityBeijingP.R.China

Background Proteins containing the Jumonji C(JmjC)domain participated in tumorigenesis and cancer ***,the mechanisms underlying this effect are still poorly *** objective was to investigate the role of Jumonji and the AT-rich interaction domain-containing 2(JARID2)—a JmjC family protein—in breast cancer,as well as its latent association with *** Immunohistochemistry,The Cancer Genome Atlas,Gene Expression Omnibus,and other databases were used to analyze the expression of JARID2 in breast cancer *** curve,5-ethynyl-2-deoxyuridine(EdU),colony formation,and cell invasion experiments were used to detect whether JARID2 affected breast cancer cell proliferation and ***-based experiments and xenotumor transplantation in NOD/SCID mice were used to examine the association between JARID2 and breast cancer ***-sequencing,Kyoto Encyclopedia of Genes and Genomes,and Gene Set Enrichment Analysis were used to identify the cell processes in which JARID2 *** purification and silver staining mass spectrometry were conducted to search for proteins that might interact with *** results were further verified using co-immunoprecipitation and glutathione S-transferase(GST)pull-down *** chromatin immunoprecipitation(ChIP)sequencing,we sought the target genes that JARID2 and metastasis-associated protein 1(MTA1)jointly regulated;the results were validated by ChIP-PCR,quantitative ChIP(qChIP)and ChIP-reChIP assays.A coculture experiment was used to explore the interactions between breast cancer cells and *** In this study,we found that JARID2 was highly expressed in multiple types of cancer including breast ***2 promoted glycolysis,lipid metabolism,proliferation,invasion,and stemness of breast cancer ***,JARID2 physically interacted with the nucleosome remodeling and deacetylase(NuRD)complex,transcriptionally repressing a series of tu

关键词： breast tumorigenesis JARID2 metabolism the NuRD complex tumor suppressor genes

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Metabolomics in human type 2 diabetes research

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Frontiers of Medicine 2013年第1期7卷 4-13页

作者： Jingyi Lu Guoxiang Xie Weiping Jia Wei Jia Shanghai Diabetes Institute Department of Endocrinology and MetabolismShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai Key Laboratory of Diabetes MellitusShanghai Clinical Center for DiabetesShanghai 200233China center for Translational Medicine Shanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China center for Translational biomedical Research University of North Carolina at GreensboroNorth Carolina Research CampusKannapolisNC 28081USA

The high prevalence of diabetes and diabetic complications has caused a huge burden on the modern *** scientific advances have led to effective strategies for preventing and treating diabetes over the past several decades,little progress has been made toward curing the disease or even getting it under control,from a public health and overall societal *** is still a lack of reliable biomarkers indicative of metabolic alterations associated with diabetes and different drug responses,highlighting the need for the development of early diagnostic and prognostic markers for diabetes and diabetic *** emergence of metabolomics has allowed researchers to systemically measure the small molecule metabolites,which are sensitive to the changes of both environmental and genetic factors and therefore,could be regarded as the link between genotypes and *** the last decade,the progression made in metabolomics has provided insightful information on disease development and disease onset *** studies using metabolomics approach coupled with statistical tools to predict incident diabetes revealed a number of metabolites that are significantly altered,including branched-chain and aromatic amino acids,such as isoleucine,leucine,valine,tyrosine and phenylalanine,as diagnostic or highly-significant predictors of future *** review summarizes the current findings of metabolomic studies in human investigations with the most common form of diabetes,type 2 diabetes.

关键词： metabolomics type 2 diabetes metabolic pathway mass spectrometry nuclear magnetic resonance(NMR)

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Current technologies to identify protein kinase substrates in high throughput

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Frontiers in Biology 2013年第2期8卷 216-227页

作者： Liang XUE W. Andy TAO department of biochemistry Purdue University West Lafayette IN 47907 USA department of Medicinal Chemistry & Molecular Pharmacology Purdue University West Lafayette IN 47907 USA department of Chemistry Purdue University West Lafayette IN 47907 USA Purdue University center for Cancer Research Purdue University West Lafayette IN 47907 USA

Since the discovery of protein phosphorylation as an important modulator of many cellular processes, the involvement of protein kinases in diseases, such as cancer, diabetes, cardiovascular diseases, and central nervous system pathologies, has been extensively documented. Our understanding of many disease pathologies at the molecular level, therefore, requires the comprehensive identification of substrates targeted by protein kinases. In this review, we focus on recent techniques for kinase substrate identification in high throughput, in particular on genetic and proteomic approaches. Each method with its inherent advantages and limitations is discussed.

关键词： phosphorylation kinase substrate in vitro kinase assay high throughput screening mass spectrometry,phosphoproteomics

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4.4 A Resolution Cryo-EM structure of human mTOR Complex 1

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Protein & Cell 2016年第12期7卷 878-887页

作者： Huirong Yang Jia Wang Mengjie Liu Xizi Chen Min Huang Dan Tan Meng-Qiu Dong Catherine C. L, Wong Jiawei Wang Yanhui Xu Hong-Wei Wang Fudan University Shanghai Cancer center Institute of Biomedical Sciences Shanghai Medical College of Fudan University Shanghai 200032 China Key Laboratory of Molecular Medicine Ministry of Education Department of Systems Biology for Medicine School of Basic Medical Sciences Shanghai Medical College of Fudan University Shanghai 200032 China State Key Laboratory of Genetic Engineering Collaborative Innovation Center of Genetics and Development School of Life Sciences Fudan University Shanghai 200433 China Ministry of Education Key Laboratory of Protein Sciences Tsinghua-Peking Joint Center for Life Sciences Beijing Advanced Innovation Center for Structural Biology School of Life Sciences Tsinghua University Beijing 100084 China National center for Protein Science Shanghai Institute of Biochemistry and Cell Biology Shanghai Institutes of Biological Sciences Chinese Academy of Sciences Shanghai 200031 China National Institute of Biological Sciences Beijing 102206 China

Mechanistic target of rapamycin （mTOR） complex 1 （mTORC1） integrates signals from growth factors, cel- lular energy levels, stress and amino acids to control cell growth and proliferation through regulating trans- lation, autophagy and metabolism. Here we determined the cryo-electron microscopy structure of human mTORC1 at 4.4 A resolution. The mTORCI comprises a dimer of heterotrimer （mTOR-Raptor-mLST8） mediated by the mTOR protein. The complex adopts a hollow rhomboid shape with 2-fold symmetry. Notably, mTORC1 shows intrinsic conformational dynamics. Within the complex, the conserved N-terminal caspase- like domain of Raptor faces toward the catalytic cavity of the kinase domain of mTOR. Raptor shows no caspase activity and therefore may bind to TOS motif for sub- strate recognition. Structural analysis indicates that FKBP12-Rapamycin may generate steric hindrance forsubstrate entry to the catalytic cavity of mTORCI. The structure provides a basis to understand the assembly of mTORC1 and a framework to characterize the regu- latory mechanism of mTORC1 pathway.

关键词： mTORC1 structure cryo-electronmicroscopy

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Crosslink between lipids and acute uveitis：a lipidomic analysis

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International Journal of Ophthalmology(English edition) 2018年第5期11卷 736-746页

作者： Hai-Yan Wang Yi Wang Yuan Zhang Jing Wang Shu-Yu Xiong Qian Sun department of Ophthalmology Shanghai First People's Hospital Affiliated to Jiaotong University Shanghai 200080China Shanghai Key Laboratory of Ocular Fundus Disease Shanghai 200080 China Shanghai Engineering center for Visual Science and Photomedicine Shanghai 200080 China department of Chemistry Fudan University Shanghai 200030 China department of Institutes of biomedical Sciences Fudan University Shanghai 200030 China

AIM：To explore the roles of phospholipids and sphingolipids in the inflammatory process of ***：Aqueous humor（AH） and the retina were obtained from endotoxin-induced uveitis（EIU） rats during the acute inflammation stage（24 h after endotoxin injection）.Lipids were extracted using a modified Bligh and Dyer method and subjected to mass spectrometric identification using class-specific lipid standards and ratiometric *** intensity analysis was performed to evaluate the amount change of common lipids between the EIU and control ***：Unique lipid species encompassing all five phospholipid classes were found in both control and the EIU AH and *** with the significantly increased level of lysophospholipids in the EIU AH and retina,we found that the ratio of lysophospholipids to total phospholipids was significantly increased *** also detected a significant increase in 18：0 lysophosphatidylcholine levels in the EIU group（fold change =6.4 in AH and 3.8 in retina）.Cer240,Cer241,and SM240 levels remarkably increased in the EIU *** C12 ceramide-1-phosphate（C12 C-1-P）,C16 C-1-P,C24 C-1-P,and upregulated Cer160,Cer240,SM120,and SM240 were found in EIU retina.C-1-P was believed to restore homeostasis by inhibiting nuclear factor kappa B（NF-κB） ***,we still found elevated NF-κB levels in the EIU ***：A variety of lipids might have played a critical role in EIU *** topical application of these protective lipids or inhibition of these pro-inflammatory lipids may be useful therapeutic strategies for the resolution of EIU.

关键词： lipidomics mass spectrometry uveitis phospholipid sphingolipid

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Polysaccharide isolated from wax apple suppresses ethyl carbamate-induced oxidative damage in human hepatocytes

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第7期24卷 574-586页

作者： Tao BAO Naymul KARIM Huihui KE Jitbanjong TANGPONG Wei CHEN department of Traditional Chinese Medicine Sir Run Run Shaw HospitalSchool of MedicineZhejiang UniversityHangzhou 310016China department of Food Science and Nutrition Zhejiang UniversityHangzhou 310058China biomedical Sciences School of Allied Health SciencesWalailak UniversityNakhon Si Thammarat 80161Thailand Ningbo Innovation center Zhejiang UniversityNingbo 315100China

Wax apple(Syzygium samarangense)has received growing research interest for its high nutritional and medicinal value due to its constituents such as polysaccharide,organic acids,flavonoids,minerals,and other *** this study,wax apple polysaccharide(WAP)was isolated from this plant and its protective effect against ethyl carbamate(EC)-induced oxidative damage was evaluated in human hepatocytes(L02 cells).Firstly,a series of analyses such as high-performance liquid chromatography(HPLC),high-performance gel permeation chromatography(HPGPC),Fourier transform infrared spectroscopy(FT-IR),gas chromatography/mass spectrometry(GC/MS),and 1H and 13C nuclear magnetic resonance(NMR)were conducted to identify the structure of,in vitro cell experiments were performed to verify the protective effects of WAP against EC-induced cytotoxicity,genotoxicity,and oxidative damage in L02 *** results revealed that WAP is composed of mannose,rhamnose,glucuronic acid,galacturonic acid,glucose,galactose,arabinose,and fucose in a molar ratio of 2.20:3.94:4.45:8.56:8.86:30.82:39.78:*** a combination of methylation and NMR spectroscopic analysis,the primary structure of WAP was identified as Araf-(1→,Glcp-(1→,→2)-Araf-(1→,→3)-Galp-(1→,→3)-Araf-(1→,and→6)-Galp-(1→.Cell experiments indicated that WAP exhibited significant protective effects on EC-treated L02 cells via suppressing cytotoxicity and genotoxicity,reducing reactive oxygen species(ROS)and O2?-formation,as well as improving mitochondrial membrane potential(MMP)and glutathione(GSH).In a nutshell,WAP has the potential as an important therapeutic agent or supplement for hepatic oxidative ***,further studies are needed to prove the above effects in vivo at the biological and clinical levels.

关键词： Wax apple polysaccharide Polysaccharide characterization Ethyl carbamate Hepatic oxidative stress

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Multiplexed Biosensing Diagnostic Platforms Detecting Autoantibodies to Tumor-Associated Antigens from Exosomes Released by CRC Cells and Tissue Samples Showed High Diagnostic Ability for Colorectal Cancer

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Engineering 2021年第10期7卷 1393-1412页

作者： Ana Montero-Calle Itziar Aranguren-Abeigon María Garranzo-Asensio Carmen Poves María Jesús Fernández-Aceñero Javier Martínez-Useros Rodrigo Sanz Jana Dziaková Javier Rodriguez-Cobos Guillermo Solís-Fernández Eloy Povedano Maria Gamella Rebeca Magnolia Torrente-Rodríguez Miren Alonso-Navarro Vivian de los Ríos J.Ignacio Casal Gemma Domínguez Ana Guzman-Aranguez Alberto Peláez-García JoséManuel Pingarrón Susana Campuzano Rodrigo Barderas Chronic Disease Program(UFIEC) Carlos III Health InstituteMadrid E-28220Spain department of biochemistry and Molecular Biology Faculty of Optics and OptometryComplutense University of MadridMadrid E-28040Spain Gastroenterology Unit San Carlos Clinical HospitalMadrid E-28040Spain Surgical Pathology department San Carlos Clinical HospitalMadrid E-28040Spain Translational Oncology Division OncoHealth InstituteJimenez Diaz Foundation University HospitalMadrid E-28040Spain department of biochemistry Faculty of MedicineAlberto Sols Institute of Biomedical ResearchCSIC-UAMMadrid E-28029Spain department of Analytical Chemistry Faculty of Chemical SciencesComplutense University of MadridMadrid E-28040Spain center for Biological Research Spanish National Research Council(CSIC)MadridE-28040Spain Molecular Pathology and Therapeutic Targets Group La Paz University Hospital(IdiPAZ)Madrid E-28046Spain

Colorectal cancer(CRC)is the second leading cause of cancer-related death *** five-year survival rate of CRC patients depends on the stage at diagnosis,being higher than 80%when CRC is diagnosed in the early stages but lower than 10%when CRC is diagnosed in advanced *** against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have been widely demonstrated to aid in early ***,we herein aim to identify autoantigens target of autoantibodies specific to CRC that possess a significant ability to discriminate between CRC patients and healthy individuals by means of liquid *** that end,we examined the protein content of the exosomes released by five CRC cell lines and tissue samples from CRC patients by means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to *** bioinformatics and meta-analysis,we selected 15 proteins that are more likely to be actual CRC autoantigens in order to evaluate their role in CRC prognosis by Western blot(WB)and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in both tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC *** validation,all but one showed a statistically significant high diagnostic ability to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either by luminescence Halotag-based beads,or by a multiplexed biosensing platform involving the use of magnetic microcarriers as solid support modified with covalently immobilized Halotag fusion proteins constructed for CRC *** together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantibody levels in plasma against the TAAs identified here

关键词： Autoantibodies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response Point of care Biosensors

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