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Investigating the role of the R213G SOD3 polymorphism in lung disease

Investigating the role of the R213G SOD3 polymorphism in lung disease
研究 R213G SOD3 多态性在肺部疾病中的作用
批准号：
8656652
负责人：
RUSSELL Paul BOWLER
金额：
$29.62万
依托单位：
NATIONAL JEWISH HEALTH
依托单位国家：
美国
项目类别：
财政年份：
2012
资助国家：
美国
项目状态：
已结题
起止时间：
2012-07-01 至 2016-04-30
来源：
https://reporter.nih.gov/project-details/8656652
关键词：
AcuteAffectAmino AcidsAnimal ModelAntioxidantsApoptoticArginineAttenuatedBase PairingBindingBiological AssayBreathingCandidate Disease GeneCardiovascular DiseasesCause of DeathCellsChronic Obstructive Airway DiseaseCigaretteCodeConfocal MicroscopyCytosineDataDevelopmentDiagnostic testsElementsEpithelialEpitheliumExcisionExtracellular FluidExtracellular MatrixExtracellular SpaceFunctional RNAGene ProteinsGenesGenetic PolymorphismGenetic Predisposition to DiseaseGlycineGoalsGuanineHereditary DiseaseHeritabilityHumanHuman GeneticsIn VitroInflammationInjuryKnock-in MouseKnock-outKnockout MiceKnowledgeLaboratoriesLeadLength of StayLipopolysaccharidesLiquid substanceLungLung diseasesMacrophage ActivationMass Spectrum AnalysisMethodsMusMyocardial InfarctionNitric OxideObservational StudyOrganOxidantsOxidative StressPlasmaPopulationPredispositionProtein BindingProteinsPulmonary EmphysemaPulmonary Function Test/Forced Expiratory Volume 1ReportingResolutionResourcesRespiratory physiologyRiskRisk FactorsRoleSignal PathwaySingle Nucleotide PolymorphismSmokeSmokerSmokingStrokeStructure of parenchyma of lungSuperoxide DismutaseTestingTimeTissuesTobacco smokeToxinUnited StatesVariantWestern Blottingantioxidant therapybiobankcigarette smokingcytokineexperienceextracellulargenetic varianthuman DNAin vivolung injurymacrophagenovel diagnosticsoverexpressionpreventprotein distributionprotein functionresearch studyresponse

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英文摘要
The rs1799895 single nucleotide polymorphism (SNP) is a non-synonymous base pair change in SOD3 that results in an arginine-to-glycine substitution (R213G) in extracellular superoxide dismutase protein (EC-SOD). This region is responsible for EC- SODs binding to extracellular matrix increases plasma levels 10-fold. The R213G SNP protects smokers from developing chronic obstructive pulmonary disease (COPD) and acute exacerbations of COPD. The goal of this proposal is to elucidate the mechanism by which the R213G protects the lung from tobacco smoke. To accomplish this aim, we have created a knock-in mouse with the identical SNP. Our methods will utilize more than a decade of experience studying the EC-SOD gene and COPD.
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