A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
批准号:
2220318
负责人:
PAUL C SIMPSON
金额:
$25.17万
依托单位国家:
美国
项目类别:
财政年份:
1989
资助国家:
美国
项目状态:
已结题
起止时间:
1989-07-01 至 1995-06-30
中文摘要
这项工作的重点是心肌肥厚的临床问题,
特别是调节这一过程的分子机制。 一个新
建立了一个研究心肌肥厚的模型系统,
无血清培养的心肌细胞。 有人提出了一个新的意见,
刺激这些细胞上的α 1-肾上腺素能受体,
儿茶酚胺去甲肾上腺素诱导细胞增大或肥大,
没有DNA合成。 α 1肾上腺素能受体是第一个
受体显示调节心肌细胞肥大。
最近的研究表明,α 1受体调节mRNA的表达
在肥大期间。 特别是,α 1刺激诱导两个
早期心脏发育特征性收缩蛋白iso-mRNAs
和体内压力负荷肥大,骨骼α-肌动蛋白同工酶mRNA和
B-肌球蛋白重链同功mRNA。 这种α 1受体效应是选择性的
并在同基因转录水平上介导。 因此
关键的问题是诱导转录的机制,
α 1受体
目前的实验将测试骨骼α-
肌动蛋白同工基因和B-肌球蛋白重链同工基因含有一个或多个
α 1响应元件,即,DNA序列需要专门为
这些基因的转录响应α 1-肾上腺素能
刺激.
两种互补的功能鉴定实验方法
提出了α 1反应元件:(1)杂交基因的转染
在瞬时测定系统中;和(2)DNA酶I超敏反应作图。
必要的克隆基因可用于开始这些实验,
初步研究证明这项工作是可行的。
长期的目标是从α-淀粉样蛋白的表达来确定细胞内的通路。
1受体对基因转录的影响。 整体
一种假说是受体刺激激活了一种预先存在的蛋白质
或与α 1反应元件结合的蛋白质,
RNA聚合酶II的转录复合物。标识
本工作中的α 1响应元件或元件将提供
为随后鉴定一种或多种蛋白质奠定基础。
英文摘要
This work is focused on the clinical problem of myocardial hypertrophy,
specifically the molecular mechanisms which regulate this process. A new
model system was developed to study hypertrophy, employing neonatal heart
myocytes in serum-free culture. The novel observation was made that
stimulation of the alpha 1-adrenergic receptor on these cells by the
catecholamine norepinephrine induces cell enlargement or hypertrophy,
without DNA synthesis. The alpha 1-adrenergic receptor is the first
receptor shown to regulate cardiac myocyte hypertrophy.
Recent work has shown that the alpha 1 receptor regulates mRNA expression
during hypertrophy. In particular, alpha 1 stimulation induces two
contractile protein iso-mRNAs characteristic of early cardiac development
and pressure-load hypertrophy in vivo, skeletal alpha-actin iso-mRNA and
B-myosin heavy chain iso-mRNA. This alpha 1 receptor effect is selective
and is mediated at the level of iso-gene transcription. Thus, the
critical question is the mechanism for induction of transcription by the
alpha 1 receptor.
The present experiments will test the hypothesis that the skeletal alpha-
actin iso-gene and the B-myosin heavy chain iso-gene contain one or more
alpha 1 response elements, i.e., DNA sequences required specifically for
transcription of these genes in response to alpha 1-adrenergic
stimulation.
Two complementary experimental approaches for functional identification
alpha 1 response elements are proposed: (1) transfection of hybrid genes
in a transient assay system; and (2) DNase I hypersensitivity mapping.
The necessary cloned genes are available to begin these experiments and
preliminary studies provide evidence that the work is feasible.
The long-range goal is to define the intracellular pathway from the alpha
1 receptor at the cell surface to gene transcription. The overall
hypothesis is that receptor stimulation activates a pre-existing protein
or proteins that binds to the alpha 1 response element in a
transcriptional complex with RNA polymerase II. Identification of an
alpha 1 response element or elements in the present work will provide the
foundation for subsequent identification of the protein or proteins.
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ShEEP Request for Ultrasound Imaging System
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批准号:9908741
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2019
-
负责人:PAUL C SIMPSON
-
依托单位:
Novel therapy for cardiotoxicity of cancer drugs
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批准号:8443184
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项目类别:
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资助金额:$0.0万
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财政年份:2012
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负责人:PAUL C SIMPSON
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依托单位:
Novel therapy for cardiotoxicity of cancer drugs
-
批准号:8598801
-
项目类别:
-
资助金额:$0.0万
-
财政年份:2012
-
负责人:PAUL C SIMPSON
-
依托单位:
Novel therapy for cardiotoxicity of cancer drugs
-
批准号:8760306
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项目类别:
-
资助金额:$0.0万
-
财政年份:2012
-
负责人:PAUL C SIMPSON
-
依托单位:
MYOCARDIAL RELAXATION AND CA++ TRANSPORT IN HYPERTROPHY
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批准号:6151319
-
项目类别:
-
资助金额:$22.48万
-
财政年份:1997
-
负责人:PAUL C SIMPSON
-
依托单位:
MYOCARDIAL RELAXATION AND CA++ TRANSPORT IN HYPERTROPHY
-
批准号:2872927
-
项目类别:
-
资助金额:$21.82万
-
财政年份:1997
-
负责人:PAUL C SIMPSON
-
依托单位:
MYOCARDIAL RELAXATION AND CA++ TRANSPORT IN HYPERTROPHY
-
批准号:6351490
-
项目类别:
-
资助金额:$23.15万
-
财政年份:1997
-
负责人:PAUL C SIMPSON
-
依托单位:
ALPHA-1 ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:2220319
-
项目类别:
-
资助金额:$27.54万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:3360228
-
项目类别:
-
资助金额:$18.54万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:3360227
-
项目类别:
-
资助金额:$18.17万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
ALPHA-1 ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:6030586
-
项目类别:
-
资助金额:$36.05万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
ALPHA-1 ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:2735149
-
项目类别:
-
资助金额:$35.01万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
ALPHA-1 ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:2445178
-
项目类别:
-
资助金额:$28.77万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:3360226
-
项目类别:
-
资助金额:$18.54万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
ALPHA-1 ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:2220320
-
项目类别:
-
资助金额:$27.95万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
A1-ADRENERGIC REGULATION OF CARDIAC GENE EXPRESSION
-
批准号:3360229
-
项目类别:
-
资助金额:$24.05万
-
财政年份:1989
-
负责人:PAUL C SIMPSON
-
依托单位:
TROPHIC EFFECTS IN ADULT HEART CELL CULTURES
-
批准号:3345755
-
项目类别:
-
资助金额:$5.0万
-
财政年份:1984
-
负责人:PAUL C SIMPSON
-
依托单位:
TROPHIC EFFECTS IN ADULT HEART CELL CULTURES
-
批准号:3345754
-
项目类别:
-
资助金额:$5.48万
-
财政年份:1984
-
负责人:PAUL C SIMPSON
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依托单位:
ALPHA-1 ADRENERGIC RECEPTOR SUBTYPE IN CARDIAC GROWTH
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批准号:2216772
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项目类别:
-
资助金额:$14.02万
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财政年份:1983
-
负责人:PAUL C SIMPSON
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依托单位:
CATECHOLAMINES AND HYPERTROPHY OF CULTURED HEART CELLS
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批准号:3342134
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项目类别:
-
资助金额:$7.43万
-
财政年份:1983
-
负责人:PAUL C SIMPSON
-
依托单位:
海外基金