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Adrenal pheochromocytoma impacts three main pathways: cysteine-methionine, pyrimidine, and tyrosine metabolism

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2024年第5期25卷 410-421页

作者： Chong LAI Qingling YANG Yunuo ZHANG Renjie GONG Majie WANG Jiankang LI Maode LAI Qingrong SUN Department of Urology the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China School of Basic Medical Sciences and Clinical Pharmacy China Pharmaceutical UniversityNanjing 210009China Department of Laboratory Medicine the First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Laboratory of Behavioral Neuroscience Ningbo Kangning HospitalNingbo Institute of Microcirculation and HenbaneSchool of MedicineNingbo UniversityNingbo 315201China Xi'an Key Laboratory of Stem Celland Regenerative Medicine Institute of Medical ResearchNorthwestern Polytechnical UniversityXi'an 710072China Department of Pathology Research Unit of Intelligence Classification of Tumor Pathology and Precision TherapyChinese Academy of Medical Sciences Key Laboratory of Disease Proteomics of Zhejiang ProvinceZhejiang University School of MedicineHangzhou 310058China

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide ***,the diagnosis of PPGLs relies on diagnostic imaging and the detection of *** this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma *** identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal *** conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were *** integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the *** analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant ***,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and *** results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

关键词： Pheochromocytoma and paraganglioma(PPGL) Metabolomics Gene set variation analysis L-Dihydroorotic acid Vanylglycol

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Author correction to‘Pharmacologically targeting molecular motor promotes mitochondrial fission for anti-cancer’[Acta Pharm Sin B 11(2021)1853–1866]

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Acta Pharmaceutica Sinica B 2024年第5期14卷 2358-2358页

作者： Yi Qian Meimei Zhao Qinghua Han Jingkang Wang Lixi Liao Heng Yang Dan Liu Pengfei Tu Hong Liang Kewu Zeng State Key Laboratory of Natural and Biomimetic Drugs School of Pharmaceutical SciencesPeking UniversityBeijing 100191China proteomics Laboratory Medical and Healthy Analytical CenterPeking University Health Science CenterBeijing 100191China

The authors regret that the representative images of tumor tissue staining for the intraperitoneal injection of J13 in the left panel of Fig.5E and G(Page 1862)were incorrect due to an inadvertent mistake of copying and pasting in the process of assembling figures with Adobe Photoshop *** our studies,at least three biological replicates were included in each treatment group and at least three images were taken for different fields of each *** corrected version of Fig.5E and G have been provided below,and the change did not affect the results and conclusions of this *** original data of these figures have been provided to the Editorial Office,and the corresponding authors or the Editorial Office can be contacted for original data access.

关键词： correction figures assembling

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PGLYRP1 protein as a novel mediator of cellular dialogue in neuroinflammation

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Neural Regeneration Research 2025年第7期20卷 1993-1994页

作者： Anup Bhusal Won-Ha Lee Kyoungho Suk Department of Pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea BK21 Plus KNU Biomedical Convergence Program Department of Biomedical ScienceSchool of MedicineKyungpook National UniversityDaeguRepublic of Korea School of Life Sciences BK21 plus KNU Creative BioResearch GroupKyungpook National UniversityDaeguRepublic of Korea Brain Science and Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

element in several neurological *** cells play a critical role in directing neuroinflammation,both in deleterious and beneficial *** communicate with one another,nearby neurons,and infiltrating cells following central nervous system(CNS)***,understanding cellular crosstalk has become fundamental to comprehending neurodegenerative conditions at the micro level(Bhusal et al.,2023).In recent times,scientists have used various transcriptomics and proteomics analyses to identify molecules that are responsible for this cellular communication and to determine the resulting functional *** molecules involved in interglial crosstalk have been identified to ***,the role of peptidoglycan recognition proteins(PGRPs)in the nervous system has received considerably less *** are a unique class of innate immune pattern recognition molecules that bind to bacterial peptidoglycans(PGN)and act as antibacterial agents(Dziarski,2004)。

关键词： inflammation al. considerably

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Deficiency of betaine-homocysteine methyltransferase activates glucose-6-phosphate dehydrogenase(G6PD)by decreasing arginine methylation of G6PD in hepatocellular carcinogenesis

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Science China(Life Sciences) 2024年第8期67卷 1648-1665页

作者： Jie Gao Xiaoyi Shi Yaohui Sun Xudong Liu Feng Zhang Chengcheng Shi Xiao Yu Zhiping Yan Long Liu Shizhe Yu Jiacheng Zhang Xiaodan Zhang Shuijun Zhang Wenzhi Guo Department of Hepatobiliary and Pancreatic Surgery The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Diagnosis&Treatment League for Hepatopathy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Henan Innovative Research group for Hepatobiliary&Pancreatic Surgery and Digestive Organ Transplantation Zhengzhou 450052China Henan Organ Transplantation Quality Control Centre Zhengzhou 450052China Henan Engineering Technology Research Center for Organ Transplantation Zhengzhou 450052China Department of Pharmacy The First Affiliated Hospital of Zhengzhou UniversityZhengzhou 450052China Department of General Surgery Huashan HospitalFudan University Shanghai 200040China Cancer Metastasis Institute Fudan UniversityShanghai 200040China

Betaine-homocysteine methyltransferase(BHMT)regulates protein methylation and is correlated with tumorigenesis;however,the effects and regulation of BHMT in hepatocarcinogenesis remain largely ***,we determined the clinical significance of BHMT in the occurrence and progression of hepatocellular carcinoma(HCC)using tissue samples from 198 *** was to be frequently found(86.6%)expressed at relatively low levels in HCC tissues and was positively correlated with the overall survival of patients with *** overexpression effectively suppressed several malignant phenotypes in hepatoma cells in vitro and in vivo,whereas complete knockout of Bhmt(Bhmt^(−/−))produced the opposite *** combined proteomics,metabolomics,and molecular biological strategies and detected that Bhmt^(−/−)promoted hepatocarcinogenesis and tumor progression by enhancing the activity of glucose-6-phosphate dehydrogenase(G6PD)and PPP metabolism in DEN-induced HCC mouse and subcutaneous tumor-bearing *** contrast,restoration of Bhmt with an AAV8-Bhmt injection or pharmacological inhibition of G6PD attenuated ***,coimmunoprecipitation identified monomethylated modifications of the G6PD,and BHMT regulated the methylation of *** sequence analysis,generation and application of specific antibodies,and site-directed mutagenesis indicated G6PD methylation at the arginine residue ***,we established bidirectionally regulated BHMT cellular models combined with methylation-deficient G6PD mutants to demonstrate that BHMT potentiated arginine methylation of G6PD,thereby inhibiting G6PD activity,which in turn suppressed *** together,this study reveals a new methylation-regulatory mechanism in hepatocarcinogenesis owing to BHMT deficiency,suggesting a potential therapeutic strategy for HCC treatment.

关键词： HCC BHMT arginine methylation G6PD PPP metabolism

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The proteome of distal nerves: implication in delayed repair and poor functional recovery

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Neural Regeneration Research 2022年第9期17卷 1998-2006页

作者： Song Guo Raymond M.Moore M.Cristine Charlesworth Kenneth L.Johnson Robert J.Spinner Anthony J.Windebank Huan Wang Department of Neurologic Surgery Mayo ClinicRochesterMNUSA Biomedical Statistics and Informatics Mayo ClinicRochesterMNUSA proteomics Core Mayo ClinicRochesterMNUSA Department of Neurology Mayo ClinicRochesterMNUSA

Chronic denervation is one of the key factors that affect nerve *** axotomy deteriorates the distal nerve stump,causes protein changes,and renders the microenvironment less permissive for *** of these factors/proteins have been individually *** better delineate the comprehensive protein expression profiles and identify proteins that contribute to or are associated with this detrimental effect,we carried out a proteomic analysis of the distal nerve using an established delayed rat sciatic nerve repair *** rats that received immediate repair after sciatic nerve transection served as control,whereas four rats in the experimental group(chronic denervation)had their sciatic nerve repaired after a 12-week *** the rats were sacrificed after 16 weeks to harvest the distal nerves for extracting ***-five micrograms of protein from each sample were fractionated in SDS-PAGE ***-MS/MS analysis was applied to the *** expression levels of nerves on the surgery side were compared to those on the contralateral *** protein with a P value of less than 0.05 and a fold change of 4 or higher was deemed differentially *** the differentially expressed proteins in both groups were further stratified according to the biological processes.A PubMed search was also conducted to identify the differentially expressed proteins that have been reported to be either beneficial or detrimental to nerve *** Pathway Analysis(IPA)software was used for pathway *** results showed that 709 differentially expressed proteins were identified in the delayed repair group,with a bigger proportion of immune and inflammatory process-related proteins and a smaller proportion of proteins related to axon regeneration and lipid metabolism in comparison to the control group where 478 differentially expressed proteins were *** experimental group also had more beneficial proteins that were d

关键词： chronic axotomy chronic denervation delayed repair distal nerve functional recovery nerve regeneration peripheral nerve prolonged denervation proteome sciatic nerve sciatic nerve transection

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An orthogonal dual-regulation strategy for sensitive biosensing applications

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National Science Review 2022年第9期9卷 246-259页

作者： Xian Yang Jinhua Wang Zhongfeng Gao Weiqi Zhang Hai Zhu Yongjun Song Quan Wang Mingjie Liu Lei Jiang Yu Huang Fan Xia State Key Laboratory of Biogeology and Environmental Geology Engineering Research Center of Nano-Geomaterials of Ministry of EducationFaculty of Material Science and ChemistryChina University of Geosciences State Grid Integrated Energy Service group CO.LTD. State Key Laboratory of proteomics Beijing Proteome Research Center National Center for Protein Sciences(Beijing)Beijing Institute of Lifeomics Shandong Provincial Key Laboratory of Detection Technology for Tumor Markers College of Chemistry and Chemical Engineering Linyi University Key Laboratory of Bio-Inspired Smart Interfacial Science and Technology of the Ministry of Education School of Chemistry and EnvironmentBeihang University Zhejiang Institute China University of Geosciences

Biosensing systems based on controllable motion behaviors of droplets have attracted extensive attention,but still face challenges of insufficient sensitivity and uncontrollable dynamic range due to imprecise manipulation of droplet motion on the ***,we report an orthogonal dual-regulation strategy for precise motion control of droplets and we demonstrate its utility as a sensitive sensing system with controllable dynamic ranges of sensing for adenosine triphosphate,miRNA,thrombin and kanamycin,as well as discrimination of five kinds of D *** endowed a DNA-contained bio-droplet sliding on a lubricant-infused structural surface with micro-grooves to separately adjust the resistance from liquid phase and solid *** resistance from liquid phase mainly depended on hydrophobic interaction between DNA and lubricant,which can be finely tuned by different DNA’s average chain ***,the resistance from solid surface was determined by the energy barrier from the periodic micro-grooves,which can be adjusted by varying the droplet’s sliding direction on the *** hydrophobic interaction is conformed to be orthogonal to the micro-grooves’ anisotropic resistance by three different *** orthogonal dual-regulation strategy thus demonstrated its ability to precisely control bio-droplets’ motion behaviors and sensitive detection with adjustable dynamic ranges for various *** dual-regulation strategy will provide significant insights for super-wettable biosensors,visual inspection and beyond.

关键词： motion behavior sensitive detection dynamic range hydrophobic interaction anisotropic resistance

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Proliferating cell nuclear antigen involved in the repair process of ouabain-induced brain damage independent of hypertension in rats

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Chinese Medical Journal 2014年第11期127卷 2111-2116页

作者： You Beian Shen Lin Qiu Jie Liu Xiangju Zhao Shaohua Ji Xiang Wang Yan Gao Haiqing Department of Geriatrics Qilu Hospital of Shandong University Shandong Provincial Key Laboratory of Cardiovascular proteomics Jinan Shandong 250012 China

Background Ouabain is a mammalian adrenocortical hormone that is involved in the pathogenesis of hypertension by inhibiting Na-K ATPase *** also participates in a variety of kinase-mediated signaling pathways associated with Na-K *** studies have shown that ouabain can cause cardiac remodeling independent of elevated blood pressure and that proliferating cell nuclear antigen （PCNA） plays a coordinating role for numerous proteins involved in multiple processes associated with DNA ***,we hypothesized that ouabain might play a role in the cerebral cortex through signaling pathways independent of *** PCNA might be involved in this *** Male Sprague-Dawley rats were treated with ouabain or with 0.9% nitric sodium as the control *** blood pressure was recorded *** four weeks of treatment,morphological changes in the cerebral cortex were analyzed using light and transmission electron *** expression of PCNA in the cerebral cortex was evaluated by immunohistochemistry,real time quantitative PCR,and Western *** After 4-week treatment,there was no significant difference in systolic blood pressure compared with the control group,but both structural deterioration and up-regulated expression of PCNA in the brain was induced by ouabain *** These results suggest that ouabain induces alterations in the brain structure,and this effect is independent of blood *** might be involved in the repair process of ouabain-induced brain damage.

关键词： ouabain proliferating cell nuclear antigen hypertension brain Na-K ATPase

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In Vivo Phosphorylation Site Mapping and Functional Characterization of Arabidopsis Phototropin 1

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Molecular Plant 2008年第1期1卷 178-194页

作者： Stuart Sullivan Catriona E. Thomson Douglas J. Lamont Matthew A. Jones John M. Christie Plant Science group Division of Biochemistry and Molecular Biology. Institute of Biomedical and Life Sciences University of Glasgow. University Avenue. Glasgow Scotland UK FingerPrints proteomics Facility Post-Genomics and Molecular Interactions Centre. School of Life Sciences MSI/WTB/CIR Complex University of Dundee. Dundee Scotland UK

Phototropins （phot1 and phot2） are blue-light receptor kinases controlling a range of responses that optimize the photosynthetic efficiency of plants. Light sensing is mediated by two flavin-binding motifs, known as LOVl and LOV2, located within the N-terminal region of the protein. Photoexcitation via LOV2 leads to activation of the C-terminal kinase domain and consequently receptor autophosphorylation. However, knowledge of the in-vivo phosphorylation sites for Arabidopsis phototropins is lacking and has impeded progress in elucidating the functional significance of receptor phos- phorylation. We have purified photl from Arabidopsis and identified the in-vivo sites of receptor phosphorylation by liquid chromatography tandem mass spectrometry. Arabidopsis-derived photl binds flavin mononucleotide as chromophore and is phosphorylated at four major sites located upstream of LOV2 （Ser^58, Ser^85, Ser^350, and Ser^410）, three of which are induced by blue light. Nevertheless, structure-function analysis indicates that the biological activity of photl can be attributed to a modular unit comprising the LOV2-kinase region of the protein. Thus, peptide regions upstream of LOV2, including the sites of receptor phosphorylation identified here, do not appear to be important for receptor signaling. By contrast, these regions may be necessary for maximizing stomatal performance and possibly light-induced relocalization of photl.

关键词： Phototropins (phot1 and phot2) lavin-binding motifs

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Phylogenetic analysis of 48 gene families revealing relationships between Hagfishes, Lampreys, and Gnathostomata

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Journal of Genetics and Genomics 2008年第5期35卷 285-290页

作者： Shuiyan Yu Weiwei Zhang Ling Li Huifang Huang Fei Ma Qingwei Li Institute of Marine Genomics ＆ proteomics Liaoning Normal University Dalian 116029 China Department of Medical Genetics China Medical University Shenyang 110001 China

It has become clear that the extant vertebrates are divided into three major groups, that is, hagfishes, lampreys, and jawed vertebrates. Morphological and molecular studies, however, have resulted in conflicting views with regard to their interrelationships. To clarify the phylogenetic relationships between them, 48 orthologous protein-coding gene families were analyzed. Even as the analysis of 34 nuclear gene families supported the monophyly of cyclostomes, the analysis of 14 mitochondrial gene families suggested a closer relationship between lampreys and gnathostomes compared to hagfishes. Lampreys were sister group of gnathostomes. The results of this study supported the cyclostomes. Choice of outgroup, tree-making methods, and software may affect the phylogenetic prediction, which may have caused much debate over the subject. Development of new methods for tackling such problems is still necessary.

关键词： phylogenetic relationship hagfish lamprey gnathostome outgroups tree-making method

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Integrative phosphoproteomics defines two biologically distinct groups of KMT2A rearranged acute myeloid leukaemia with different drug response phenotypes

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Signal Transduction and Targeted Therapy 2023年第3期8卷 1318-1331页

作者： Pedro Casado Ana Rio-Machin Juho JMiettinen Findlay Bewicke-Copley Kevin Rouault-Pierre Szilvia Krizsan Alun Parsons Vinothini Rajeeve Farideh Miraki-Moud David CTaussig Csaba Bödör John Gribben Caroline Heckman Jude Fitzgibbon Pedro R.Cutillas Cell Signalling and proteomics group Centre for Genomics and Computational BiologyBarts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Centre for Genomics and Computational Biology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK Institute for Molecular Medicine Finland-FIMM HiLIFE-Helsinki Institute of Life ScienceiCAN Digital Precision Cancer Medicine FlagshipUniversity of HelsinkiHelsinkiFinland Centre for Haemato-Oncology Barts Cancer InstituteQueen Mary University of LondonLondon EC1M6BQUK HCEMM-SU Molecular Oncohematology Research group 1st Department of Pathology and Experimental Cancer ResearchSemmelweis University BudapestBudapestHungary Cancer Research UK Cancer Therapeutics Unit Division of Cancer TherapeuticsThe Institute of Cancer ResearchSuttonUK a The Alan Turing Institute The British Library2QR96 Euston RdLondon NW12DBUK

Acute myeloid leukaemia(AML)patients harbouring certain chromosome abnormalities have particularly adverse *** these patients,targeted therapies have not yet made a significant clinical *** understand the molecular landscape of poor prognosis AML we profiled 74 patients from two different centres(in UK and Finland)at the proteomic,phosphoproteomic and drug response phenotypic *** data were complemented with transcriptomics analysis for 39 *** integration highlighted a phosphoproteomics signature that define two biologically distinct groups of KMT2A rearranged leukaemia,which we term MLLGA and *** presented increased DOT1L phosphorylation,HOXA gene expression,CDK1 activity and phosphorylation of proteins involved in RNA metabolism,replication and DNA damage when compared to MLLGB and no KMT2A rearranged *** was particularly sensitive to 15 compounds including genotoxic drugs and inhibitors of mitotic kinases and inosine-5-monosphosphate dehydrogenase(IMPDH)relative to other ***-risk KMT2A-MLLT3 cases were mainly represented in a third group closer to MLLGA than to *** expression of IMPDH2 and multiple nucleolar proteins was higher in MLLGA and correlated with the response to IMPDH inhibition in KMT2A rearranged leukaemia,suggesting a role of the nucleolar activity in sensitivity to *** summary,our multilayer molecular profiling of AML with poor prognosis and KMT2A-MLLT3 karyotypes identified a phosphoproteomics signature that defines two biologically and phenotypically distinct groups of KMT2A rearranged *** data provide a rationale for the potential development of specific therapies for AML patients characterised by the MLLGA phosphoproteomics signature identified in this study.

关键词： metabolism signature biologically

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