Post-translational Modification of Cx43 Regulates Myometrial Quiescence
Cx43 的翻译后修饰调节子宫肌层静止
基本信息
- 批准号:10575364
- 负责人:
- 金额:$ 21.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-02-15 至 2025-01-31
- 项目状态:未结题
- 来源:
- 关键词:AcuteAffectAfrican AmericanAfrican American populationAgonistBirthBlood flowC-terminalCaucasiansCellsCessation of lifeConnexin 43CouplingCyclic AMPCyclic GMPCysteineCytosolDevelopmentDisparateDose LimitingEthnic OriginFDA approvedFetusFunctional disorderFutureGap JunctionsGenerationsGiant CellsHourHumanLabelLabor OnsetLinkMaintenanceMeasuresMechanicsMediatingMedicalMembraneMethodsModificationMothersMuscle CellsMuscle relaxation phaseMutateMutationMyometrialNitric OxideNitrosationOutcomeOutcomes ResearchOxidoreductasePathway interactionsPharmaceutical PreparationsPharmacologyPhosphorylationPositioning AttributePost-Translational Protein ProcessingPost-Translational RegulationPregnancyPregnant UterusPregnant WomenPremature BirthPremature InfantPremature LaborPropertyProtein KinaseRegulationRelaxationResearchRiskRoleS-NitrosoglutathioneSerineSiteSmooth MuscleSmooth Muscle MyocytesStretchingTerbutalineTestingTherapeuticTimeTissuesTocolysisTocolytic AgentsUterusVascular Endothelial CellWomandisabilityextreme prematuritygap junction channelhealth disparityinnovationinterestmonolayermutantmyometriumnoveloverexpressionpharmacologicpregnantpreventprotein expressionprotein kinase C epsilonresponsetranslational approachuterine smooth muscle cell
项目摘要
PROJECT SUMMARY ABSTRACT
Preterm birth is a major medical problem resulting in disability and death for very preterm infants. Therapeutic approaches
to manage preterm labor are off-label and ineffective. No tocolytic therapy in use today is satisfactory beyond 48 hours, and
none are FDA approved. Preterm labor more often impacts African American women than their Caucasian counterparts.
We seek to understand the dysfunctional relaxation of the myometrium that leads to preterm labor and resulting preterm
birth. Our central hypothesis is that nitric oxide is generated locally within the myometrium by microvascular endothelial
cells as a result of mechanical stretch and increased blood flow to the expanding uterus. Nitric oxide S-nitrosates Cx43 in
the muscle cell. Cx43 S-nitrosation promotes C-terminal phosphorylation that holds Cx43 in its hemichannel state and
favors muscle cell quiescence. Hemichannels form gap junctions at the time of labor. Gap junctions are a feature of activated
myometrium. Promoting connexin 43 S-nitrosation offers a unique target for tocolytic development. Translational
approaches in human pregnancy tissues are essential if we are to discover and exploit the unique mechanisms that subserve
uterine quiescence during pregnancy and their dysregulation in preterm labor.
项目摘要
早产是导致非常早产儿残疾和死亡的主要医学问题。治疗方法
治疗早产的药物都是标签外的,无效的。目前使用的宫缩抑制疗法在48小时以上都不能令人满意,
没有一个是FDA批准的。早产更经常影响非洲裔美国妇女比他们的白人同行。
我们试图了解子宫肌层松弛功能失调导致早产和由此导致的早产
出生我们的中心假设是,一氧化氮是由微血管内皮细胞在子宫肌层局部产生的。
由于机械拉伸和增加的血液流向扩张的子宫,一氧化氮S-亚硝化Cx43
肌肉细胞。Cx43 S-亚硝化促进C-末端磷酸化,使Cx43保持在其半通道状态,
有利于肌肉细胞静止半通道在分娩时形成缝隙连接。缝隙连接是一种激活的
子宫肌层促进连接蛋白43 S-亚硝化为宫缩抑制发育提供了独特的靶点。平移
如果我们要发现和利用这种独特的机制,
妊娠期子宫静止和早产时的失调。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('IAIN L BUXTON', 18)}}的其他基金
Regulation of CAP Protein S-Nitrosation in Preterm Labor
早产中 CAP 蛋白 S-亚硝化的调节
- 批准号:
10221011 - 财政年份:2018
- 资助金额:
$ 21.99万 - 项目类别:
Regulation of CAP Protein S-Nitrosation in Preterm Labor
早产中 CAP 蛋白 S-亚硝化的调节
- 批准号:
10002335 - 财政年份:2018
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
8138103 - 财政年份:2010
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
7599726 - 财政年份:2007
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
7781360 - 财政年份:2007
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
8044194 - 财政年份:2007
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
7201882 - 财政年份:2007
- 资助金额:
$ 21.99万 - 项目类别:
REGULATION OF MYOMETRIAL RELAXATION: AGONIST-SPECIFIC cGMP ACTION
子宫肌层松弛的调节:激动剂特异性 cGMP 作用
- 批准号:
7369765 - 财政年份:2007
- 资助金额:
$ 21.99万 - 项目类别:
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