Heme allocation and disruptions in asthma and the failing heart
Heme allocation and disruptions in asthma and the failing heart
批准号:
10516435
负责人:
Elizabeth A. Sweeny
金额:
$24.9万
依托单位国家:
美国
项目类别:
财政年份:
2022
资助国家:
美国
项目状态:
已结题
起止时间:
2022-01-01 至 2024-12-31
中文摘要
血红素蛋白NADPH氧化酶5 (NOX5)是一种跨膜信号转导酶
英文摘要
The heme protein NADPH oxidase 5 (NOX5) is a transmembrane signaling enzyme which produces
superoxide in response to elevated intracellular calcium levels and is emerging as an exciting player in
immunity and the cardiovascular system. NOX5 is crucial for proper vascular contraction and appears to be
a nexus between cellular redox and calcium signaling, As the most recently discovered member of the
NOX family of enzymes, details of NOX5 regulation and its role in the cell remain poorly resolved. It has,
however, been implicated in numerous human diseases including cancers, diabetes and cardiovascular
disorders. Elucidating details of NOX5 regulation and its role in cardiovascular health and disease is crucial
to our understanding of normal cellular functions and how these become disrupted in disease. Based on
preliminary data from the K99 phase, the R00 phase will focus on investigating the role of NOX5 in
cardiomyocyte function and its contribution to the initiation and progression of atrial fibrillation (AF) (Aim 1)
and to probe the significance of novel protein:protein interactions identified in the K99 phase which link
NOX5 and the actin cytoskeleton, mitochondria, RNA regulation and stress response systems (Aim 2). Aim
1 will focus on understanding how NOX5 knockdown and overexpression affect gene and protein
expression, calcium flux, and cellular metabolism in induced pluripotent stem cell (iPSC) derived
cardiomyocytes, and then using patient tissue from hearts in AF or sinus rhythm to test hypothesizes
generated from the iPSC derived cardiomyocyte system. Aim 2 will use a model cell system (HEK293 cells
and HEK293 cells overexpressing NOX5) as well as iPSC derived cardiomyocytes to probe the interactome
of NOX5 in response to stimuli and to understand how these interactions affect NOX5 activity and
localization, the actin cytoskeleton, calcium flux, cellular metabolism, gene expression and the stress
response system. This project will uncover crucial details about the role of NOX5 in the heart and in the
broader context of cellular homeostasis. It will also lay important groundwork for identifying molecular
factors responsible for the switch between physiological and pathological responses and identify
interactions and interaction networks ideal for further study using purified components for use in
reconstitution assays, structural biology projects, mechanistic studies using biochemical approaches and
drug discovery projects.
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Heme allocation and disruptions in asthma and the failing heart
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批准号:10542447
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项目类别:
-
资助金额:$24.9万
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财政年份:2022
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负责人:Elizabeth A. Sweeny
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依托单位:
国内基金
海外基金
CREB在杏仁核神经环路memory allocation中的作用和机制研究
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批准号:31171079
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项目类别:面上项目
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资助金额:55.0万元
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批准年份:2011
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负责人:周宇
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依托单位:
协同中继系统跨层资源分配与优化调度的理论及方法
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批准号:60972070
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项目类别:面上项目
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资助金额:33.0万元
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批准年份:2009
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负责人:陈前斌
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依托单位: