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Proteomic analysis of human frontal and temporal cortex using iTRAQ-based 2D LCMS/MS

Chinese Neurosurgical Journal 2021年第4期7卷 236-248页

作者： Long Xu Haidan Sun Yang Zhang Zhengguang Guo Xiaoping Xiao Xin Zhou Kun Hu Wei Sun Bo Wang Weiming Liu Department of Neurosurgery Beijing Tiantan HospitalCapital Medical UniversityNo.119 West RoadSouth Fourth Ring RoadBeijing 100070China China National Clinical Research Center for Neurological Diseases(NCRC-ND) Beijing 100070China Core Facility of Instrument School of Basic Medicine Chinese Academy of Medical SciencesInstitute of Basic Medicine Peking Union Medical College5 Dong Dan San TiaoBeijing 100005China State Key Laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of Sciences15 Datun RoadBeijing 100101China

Background:The human brain is the most complex organ in the body,and it is important to have a better understanding of how the protein composition in the brain regions contributes to the pathogenesis of associated neurological disorders.Methods:In this study,a comparative analysis of the frontal and temporal cortex proteomes was conducted by isobaric tags of relative and absolute quantification(iTRAQ)labeling and two-dimensional liquid chromatographytandem mass spectrometry(2D LC-MS/MS).Brain protein was taken from relatively normal tissue that could not be avoided of damage during emergent surgery of the TBI(traumatic brain injury)patients admitted in Beijing Tiantan Hospital from 2014 to 2017.Eight cases were included.Four frontal lobes and 4 temporal lobes proteome were analyzed and the proteins were quantitated.Gene Ontology(GO),Ingenuity Pathway Analysis(IPA),and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were used to analyze the biological function of identified proteins,unchanged proteins,and differentially expressed proteins(DEPs).Results:A total number of 2127 protein groups were identified in the frontal and temporal lobe proteomes.A total of 1709 proteins could be quantitated in both the frontal and temporal cortex.Among 90 DEPs,14 proteins were screened highly expressed in the temporal cortex,including MAPT,SNCG,ATP5IF1,GAP43,HSPE1,STMN1,NDUFS6,LDHB,SNCB,NDUFA7,MRPS36,EPDR1,CISD1,and RALA.In addition,compared to proteins expressed in the frontal cortex,14 proteins including EDC4,NIT2,VWF,ASTN1,TGM2,SSB,CLU,HBA1,STOM,CRP,LRG1,SAA2,S100A4,and VTN were a low expression in the temporal cortex.The biological process enrichment showed that unchanged proteins between the frontal and temporal cortex mainly take part in regulated exocytosis,axon guidance,and vesicle-mediated transport.The KEGG pathway analysis showed that unchanged proteins between the frontal and temporal cortex mainly take part in oxidative phosphorylation,carbon metabolism,Huntington’s disease,and Parkinson’s disease.Conc

关键词： Frontal cortex temporal cortex iTRAQ Proteomics 2D-LC-MS/MS

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Expression of iron-related proteins and alterations in iron content in the temporal cortex of parkinsonian patients

Expression of iron-related proteins and alterations in iron ...

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中国神经科学学会第九届全国学术会议暨第五次会员代表大会

作者： Xiao-Jun YU,Ting-Ting DU,Ning SONG,Qing HE,Hong JIANG,Jun-Xia XIE~* Department of Physiology,Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines:Physiology,Medical College of Qingdao University,Qingdao 266071,China

＜正＞Objective It has been reported that iron increases in single DAergic neurons in the substantia nigra（SN） of postmortem parkinsonian patients,indicating that primary changes in neuronal iron could lead to neurodegeneration in Parkinson’s disease（PD）.However,the mechanism underlying this selective iron accumulation is largely unknown. Our previous studies in PD animal models showed iron import protein divalent metal transporter 1（DMT1） and iron export protein ferroportinl（Fpl） were all involved in the nigral iron accumulation.In the present study,we investigated the expression of iron-related proteins（DMT1,Fpl and IRP1） and alterations in iron content in the temporal cortex of postmortem parkinsonian patients.Methods Iron concentration was measured by an inductively coupled plasma（ICP-2） detector.The expression levels of IRP1,DMT1 and Fpl were determined by western blots. Results The iron levels were significantly lower in PD patients than that of age-matched controls.The expression levels of DMT 1,Fpl and IRP1 were decreased in temporal cortex of PD patients.Conclusion This is the first time to investigate the involvement of pallium’s iron metabolism in the brains of PD patients.These results suggest that there might be a redistribution of iron in PD brains,especially between temporal cortex and SN.

关键词： temporal cortex iron Parkinson’s disease divalent metal transporter1 ferroportin1

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