FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
批准号:
6796312
负责人:
JOHN C MC GIFF
金额:
$31.48万
依托单位:
依托单位国家:
美国
项目类别:
财政年份:
2003
资助国家:
美国
项目状态:
已结题
起止时间:
2003-09-01 至 2005-08-31
关键词:
adrenalectomy angiotensin II arachidonate cytochrome P450 dietary sodium eicosanoid metabolism enzyme activity enzyme mechanism glucocorticoids hormone regulation /control mechanism hypertension isolation perfusion kidney function laboratory rat mass spectrometry nitric oxide nitric oxide synthase nutrition related tag prostaglandin endoperoxide synthase protein protein interaction tumor necrosis factor alpha vasomotion
中文摘要
20-羟基二十碳四烯酸(20-HETE)是关键肾结构的主要类二十烷酸,其中它在肾血管和肾小管功能的调节中起重要组分的作用。鉴于20-HETE对肾功能的重要性,对控制20-HETE的产生和活性的那些因素的鉴定和表征具有高度优先性,因为它们决定了类二十烷酸的肾作用的深度和广度。环氧合酶(考克斯-1和考克斯2)和一氧化氮合酶(NOS)已被确定为分别调节20-HETE代谢和产生的中心。三个目的将阐述考克斯和NO对肾脏中20-HETE水平和活性的假定重要性。目的1建立高血压AII输注模型,探讨细胞因子NO和考克斯(1和2)对20-HETE产生和生物学活性的影响及其相互关系。目的2利用高盐摄入对NO产生和低盐摄入对皮质考克斯-2表达的相对选择性作用,以研究它们对20-HETE组织水平和皮质中20-HETE代谢物的生物活性谱的单独作用。目的3:阐明糖皮质激素对TAL中考克斯- 2表达的强大负面影响,以确定涉及TNF和考克斯-2(可能还有iNOS)肾上腺后的相互作用,并将这些因素中的一种或多种与假定的CYP 450 AA代谢抑制和肾功能变化相关。
英文摘要
20-hydroxyeicosatetraenoic acid (20-HETE) is the principal eicosanoid of key renal structures where it serves an essential component in the regulation of renal vascular and tubular function. In view of the importance of 20-HETE to renal function, the identification and characterization of those factors that govern production and activity of 20-HETE assume a high priority as they determine the depth and breadth of the renal actions of the eicosanoid. Cyclooxygenases (COX-1 and COX 2) and nitric oxide synthases (NOS) have been identified as being central to the regulation of 20-HETE metabolism and production, respectively. Three Aims will address the postulated importance of COX and NO to 20-HETE levels and activities in the kidney. AIM 1 makes of the AII infusion model of hypertension to determine relationship and possible interactions of cytokines, NO and COX (both-1 and -2) that affect production and biological activities of 20-HETE. Aim 2 draws upon the relatively selective effect of high salt intake on NO production and low salt intake on cortical COX-2 expression in order to study their separate effects on 20-HETE tissue levels and spectrum of biological activities of 20-HETE metabolites in the cortex. AIM 3 addresses the powerful negative effect of glucocorticoids on COX- 2 expression in the TAL in order to define interactions involving TNF and COX-2 (and possibly iNOS) post-adrenal and to relate one or more of these factors to a postulated depression of CYP450 AA metabolism and to changes in renal function.
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FUNCTION AND REGULATION OF TRANS-EETS
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批准号:7137839
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项目类别:
-
资助金额:$48.27万
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财政年份:2005
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负责人:JOHN C MC GIFF
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依托单位:
FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
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批准号:6653341
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项目类别:
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资助金额:$31.48万
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财政年份:2002
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负责人:JOHN C MC GIFF
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依托单位:
FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
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批准号:6500476
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项目类别:
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资助金额:$31.48万
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财政年份:2001
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负责人:JOHN C MC GIFF
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依托单位:
FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
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批准号:6578852
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项目类别:
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资助金额:$31.48万
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财政年份:2001
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负责人:JOHN C MC GIFF
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依托单位:
FUNCTIONAL SIGNIFICANCE OF CYTOCHROME P450 CYCLOOXYGENASE
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批准号:6353521
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项目类别:
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资助金额:$31.48万
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财政年份:2000
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负责人:JOHN C MC GIFF
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依托单位:
CYTOCHROME P450 DEPENDENT ARACHIDONATE METABOLITES AND HYPERTENSION
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批准号:6202238
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项目类别:
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资助金额:$24.35万
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财政年份:1999
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负责人:JOHN C MC GIFF
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依托单位:
CYTOCHROME P450 DEPENDENT ARACHIDONATE METABOLITES AND HYPERTENSION
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批准号:6109759
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项目类别:
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资助金额:$24.35万
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财政年份:1998
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负责人:JOHN C MC GIFF
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依托单位:
ALL EFFECT ON ION TRANSPORT--AA METABOLITES INTERACTION
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批准号:2685843
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项目类别:
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资助金额:$2.52万
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财政年份:1997
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负责人:JOHN C MC GIFF
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依托单位:
ALL EFFECT ON ION TRANSPORT--AA METABOLITES INTERACTION
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批准号:2901499
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项目类别:
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资助金额:$2.52万
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财政年份:1997
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负责人:JOHN C MC GIFF
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依托单位:
ALL EFFECT ON ION TRANSPORT--AA METABOLITES INTERACTION
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批准号:2042415
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项目类别:
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资助金额:$2.52万
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财政年份:1997
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负责人:JOHN C MC GIFF
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依托单位:
CYTOCHROME P450 DEPENDENT ARACHIDONATE METABOLITES AND HYPERTENSION
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批准号:6241859
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项目类别:
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资助金额:$23.54万
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财政年份:1997
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098356
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项目类别:
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资助金额:$78.66万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098358
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项目类别:
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资助金额:$85.37万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098354
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项目类别:
-
资助金额:$78.14万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098353
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项目类别:
-
资助金额:$81.48万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098350
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项目类别:
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资助金额:$84.02万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098357
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项目类别:
-
资助金额:$77.28万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098349
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项目类别:
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资助金额:$65.9万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098355
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项目类别:
-
资助金额:$82.08万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
HORMONAL REGULATION OF BLOOD PRESSURE
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批准号:3098352
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项目类别:
-
资助金额:$76.67万
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财政年份:1985
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负责人:JOHN C MC GIFF
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依托单位:
海外基金