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CALRETICULIN REGULATION OF LUNG ENDOTHELIAL CELL NOS

钙网蛋白对肺内皮细胞 NOS 的调节

基本信息

批准号：
6831653
负责人：
JAWAHARLAL M. PATEL
金额：
$ 25万
依托单位：
UNIVERSITY OF FLORIDA
依托单位国家：
美国
项目类别：
财政年份：
2002
资助国家：
美国
起止时间：
2002-01-25 至 2006-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/6831653
关键词：
calreticulin cyclic GMP electron transport enzyme activity isozymes nitric oxide synthase protein protein interaction protein structure function pulmonary artery vascular endothelium vasomotion

项目摘要

DESCRIPTION (provided by applicant): Increased synthesis of a multifunctional calcium (Ca2+) binding protein calreticulin (CRT) has been reported under diverse physiologic and pathophysiologic conditions in various tissues including vascular endothelium. We recently reported that angiotensin IV-stimulated increased expression of CRT in lung endothelial cells and the protein-protein interaction between CRT and the endothelial cell isoform of nitric oxide synthase (eNOS) are causally associated with sustained (> 12 hr) activation of eNOS at a post-transcriptional level. The molecular mechanisms of CRT-mediated sustained activation of eNOS appear distinctly unique since all other known post-transcriptional mechanisms involved in activation of eNOS cause only limited or transient activation. At present CRT knows nothing about the molecular interaction and regulation of the catalytic activity of eNOS. Based on our earlier report and preliminary data, we hypothesize that the interaction of CRT with the electron transfer control element (ETE) of eNOS overrides its putative autoinhibitory function resulting in enhanced electron transfer and sustained activation of eNOS, NO/cyclic guanosine 5'-monophosphate (cGMP) production and vasorelaxation response. To test this hypothesis, we will 1) determine whether CRT interaction with ETE in the reductase domain of eNOS is causally associated with increased electron transfer and catalytic activity of eNOS, 2) characterize the molecular interaction between CRT's distinct N-domain, or P-domain (high affinity Ca2+ binding site), or C-domain (low affinity Ca2+ binding site) and ETE responsible for enhanced catalytic activity of eNOS, and 3) verify whether increased expression of CRT or its discrete domains in isolated endothelial cells and in pulmonary artery segments enhances eNOS activity, NO/cGMP production, and vasorelaxation. Identification of a molecular interaction between ETE of eNOS and CRT that causes sustained activation of eNOS will advance our understanding of eNOS regulation for maintaining pulmonary vascular function in context with increased CRT expression under diverse physiologic and pathophysiologic conditions.

描述（由申请人提供）：一种多功能钙（Ca2+）结合蛋白钙网蛋白（CRT）的合成增加已被报道

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Nitric oxide-induced persistent inhibition and nitrosylation of active site cysteine residues of mitochondrial cytochrome-c oxidase in lung endothelial cells.

一氧化氮诱导肺内皮细胞线粒体细胞色素 C 氧化酶活性位点半胱氨酸残基的持续抑制和亚硝基化。

DOI：
10.1152/ajpcell.00325.2004
发表时间：
2005
期刊：
American journal of physiology. Cell physiology
影响因子：
0
作者：
Zhang,Jianliang;Jin,Bilian;Li,Liuzhe;Block,EdwardR;Patel,JawaharlalM
通讯作者：
Patel,JawaharlalM

A cellular model to mimic exhaled cigarette smokeinduced lung microvascular endothelial cell injury and death.

模拟呼出的香烟烟雾引起的肺微血管内皮细胞损伤和死亡的细胞模型。

DOI：
发表时间：
2010
期刊：
International journal of clinical and experimental medicine
影响因子：
0.1
作者：
Zhang,Jianliang;Juedes,Noah;Narayan,VikramM;Yue,Bingfang;Rockwood,AlanL;Palma,NadiaL;Patel,JawaharlalM
通讯作者：
Patel,JawaharlalM

Role of the CX3CL1-CX3CR1 axis in chronic inflammatory lung diseases.