Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8
环核苷酸磷酸二酯酶 8 对细胞功能的调节
基本信息
- 批准号:7806124
- 负责人:
- 金额:$ 48.36万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2009
- 资助国家:美国
- 起止时间:2009-09-30 至 2011-08-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAdenylate CyclaseAdipocytesAdipose tissueAdrenal CortexAdrenal Cortex HormonesAdrenal GlandsAdultAffectAgonistAldosteroneAnimalsAnti-Arrhythmia AgentsArrhythmiaBlood PressureBrown FatCalciumCardiacCardiac Function StudyCardiac MyocytesCell FractionCell physiologyCellsCholesterol HomeostasisChronicCoupledCouplingCyclic AMPCyclic AMP-Dependent Protein KinasesCyclic NucleotidesDataDrug RegulationsEchocardiographyEnzymesEventFatty acid glycerol estersGenesHeartHeart RateHepatocyteHistocompatibility TestingHormonesImageInstitutesIsoenzymesKnockout MiceL-Type Calcium ChannelsLipidsLipolysisLiverMeasurementMeasuresMediatingMedicineMissionMitochondriaMolecularMusMyocardial InfarctionPathway interactionsPharmaceutical PreparationsPhenotypePhosphorylationProcessProductionPropertyProtein KinasePublic HealthRegulationResearchRoleRyanodine Receptor Calcium Release ChannelRyanodine ReceptorsSarcoplasmic ReticulumSteroidsTelemetryTestingThermogenesisTissuesWorkZona Fasciculataawakebaseexpectationhormone regulationin vivoinhibitor/antagonistparent grantphospholambanphosphoric diester hydrolasepolypeptidepublic health relevanceresponseuptake
项目摘要
DESCRIPTION (provided by applicant): In this supplementary research request we propose to expand the scope and accelerate the rate of progress on our project GM083926, entitled "Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8". The parent grant contains 3 specific aims, to determine the functions and mechanisms of action of PDE8s in adrenal, liver, and brown fat tissues. These are three of the tissue types in which this PDE isozyme is highly expressed.
Recently, we have found that PDE8A is also highly expressed in cardiac myocytes. Moreover, our preliminary data strongly suggest that ablation of PDE8 can modulate calcium handling in isolated cardiocytes. The focus of the proposed studies will be to determine the overall cardiac phenotype of the PDE8A knockout mouse and to identify the mechanism(s) by which PDE8 regulates calcium transients in the heart. Emphasis will be placed on the roles of PDE8A in controlling cAMP dependent phosphorylation events in isolated cardiomyocytes. We will also study the effects of the gene disruption on calcium regulation in isolated cardiomyocytes and on in vivo measurements of cardiac function.
The mission of the Institute of General Medicine is clearly relevant to studies on the mechanisms of control of cardiac function by modulation of calcium in the heart. The possibilities for developing an anti-arrhythmic drug based on modulation of PDE8 activity would seem quite real.
PUBLIC HEALTH RELEVANCE: In this supplementary research request we propose to expand the scope and accelerate the rate of progress on our project GM083926, entitled "Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8". The focus of the proposed studies will be to determine the overall cardiac phenotype of the PDE8A knockout mouse and to identify the mechanism(s) by which PDE8 regulates calcium transients in the heart. Emphasis will be placed on the roles of PDE8A in controlling cAMP-dependent phosphorylation events in isolated cardiomyocytes. We will also study the effects of the gene disruption on in vivo measurements of cardiac function.
These studies are potentially directly relevant to drug regulation of cardiac function. For example, if validated by these studies, it would appear that a drug that acted as a PDE8 activator would likely have anti-arrhythmic activity. Since most heart attacks have an arrhythmia component the relevance to public health is obvious.
描述(由申请人提供):在这份补充研究申请中,我们建议扩大范围并加快我们的项目GM083926的进展速度,该项目名为“环核苷酸磷酸二酯酶8调节细胞功能”。父母资助有三个具体目标,确定PDE8s在肾上腺、肝脏和棕色脂肪组织中的功能和作用机制。这是三种PDE同工酶高度表达的组织类型。
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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Joseph A Beavo其他文献
Cyclic nucleotide phosphodiesterases – 40 years of progress
- DOI:
10.1186/1471-2210-9-s1-s3 - 发表时间:
2009-08-11 - 期刊:
- 影响因子:2.700
- 作者:
Joseph A Beavo;James Surapisitchat;Candance Parchen - 通讯作者:
Candance Parchen
Bacterial GAF domains
- DOI:
10.1186/1471-2210-5-s1-s17 - 发表时间:
2005-06-16 - 期刊:
- 影响因子:2.700
- 作者:
Joachim E Schultz;Sandra Bruder;Anita Schultz;Sergio E Martinez;Ning Zheng;Joseph A Beavo - 通讯作者:
Joseph A Beavo
Regulation of cyclic nucleotide hydrolysis by cGMP
- DOI:
10.1186/1471-2210-5-s1-s9 - 发表时间:
2005-06-16 - 期刊:
- 影响因子:2.700
- 作者:
Joseph A Beavo - 通讯作者:
Joseph A Beavo
Specificity of commonly used cyclic nucleotides with PKA, PKG and Epac-implementing microcalorimetry to determine PDE activities
- DOI:
10.1186/1471-2210-7-s1-s25 - 发表时间:
2007-07-25 - 期刊:
- 影响因子:2.700
- 作者:
Joseph A Beavo;Johannes L Bos;Elke Butt;Stein O Doskeland;Hans-Gottfried Genieser;Thomas R Hinds;Heiko Poppe;Holger Rehmann;Sergei D Rybalkin;Frank Schwede;Xiao-Bo Tang - 通讯作者:
Xiao-Bo Tang
Molecular targets for PDE inhibitor-mediated improvement of cardiac dysfunction in the mdx mouse?
- DOI:
10.1186/1471-2210-11-s1-o20 - 发表时间:
2011-08-01 - 期刊:
- 影响因子:2.700
- 作者:
Candace M Adamo;Dao-Fu Dai;Justin M Percival;Elina Minami;Monte S Willis;Enrico Patrucco;Sergei D Rybalkin;Stanley C Froehner;Joseph A Beavo - 通讯作者:
Joseph A Beavo
Joseph A Beavo的其他文献
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{{ truncateString('Joseph A Beavo', 18)}}的其他基金
Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
肌营养不良症中高尔基体相关的 NO-cGMP 信号缺陷
- 批准号:
7941082 - 财政年份:2009
- 资助金额:
$ 48.36万 - 项目类别:
Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
肌营养不良症中高尔基体相关的 NO-cGMP 信号缺陷
- 批准号:
8516460 - 财政年份:2009
- 资助金额:
$ 48.36万 - 项目类别:
Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
肌营养不良症中高尔基体相关的 NO-cGMP 信号缺陷
- 批准号:
8303029 - 财政年份:2009
- 资助金额:
$ 48.36万 - 项目类别:
Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
肌营养不良症中高尔基体相关的 NO-cGMP 信号缺陷
- 批准号:
7781662 - 财政年份:2009
- 资助金额:
$ 48.36万 - 项目类别:
Golgi-associated NO-cGMP Signaling Defect in Muscular Dystrophy
肌营养不良症中高尔基体相关的 NO-cGMP 信号缺陷
- 批准号:
8118226 - 财政年份:2009
- 资助金额:
$ 48.36万 - 项目类别:
Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8
环核苷酸磷酸二酯酶 8 对细胞功能的调节
- 批准号:
8072053 - 财政年份:2008
- 资助金额:
$ 48.36万 - 项目类别:
Regulation of Cellular Functions by Cyclic Nucleotide Phosphodiesterase 8
环核苷酸磷酸二酯酶 8 对细胞功能的调节
- 批准号:
7525488 - 财政年份:2008
- 资助金额:
$ 48.36万 - 项目类别:
Phosphodiesterase 8 Synergies: Regulation of Brown Fat, and Cardiac Functions
磷酸二酯酶 8 协同作用:棕色脂肪和心脏功能的调节
- 批准号:
8510658 - 财政年份:2008
- 资助金额:
$ 48.36万 - 项目类别:
Phosphodiesterase 8 Synergies: Regulation of Brown Fat, and Cardiac Functions
磷酸二酯酶 8 协同作用:棕色脂肪和心脏功能的调节
- 批准号:
8676811 - 财政年份:2008
- 资助金额:
$ 48.36万 - 项目类别:
Phosphodiesterase 8 Synergies: Regulation of Brown Fat, and Cardiac Functions
磷酸二酯酶 8 协同作用:棕色脂肪和心脏功能的调节
- 批准号:
8914758 - 财政年份:2008
- 资助金额:
$ 48.36万 - 项目类别:
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