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Transcriptional Regulation of KCNH2

KCNH2 的转录调控

基本信息

批准号：
10366053
负责人：
Brian P Delisle
金额：
$ 57.1万
依托单位：
UNIVERSITY OF KENTUCKY
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-03-08 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10366053
关键词：
ARNTL gene Action Potentials Adverse event Arrhythmia Biological Assay Bioluminescence Brain Cardiac Cardiac Electrophysiologic Techniques Cardiac Myocytes Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cells Cessation of life Chemistry Chronic Chronobiology Circadian Rhythms Cues Data Electrophoretic Mobility Shift Assay Elements Environment Gene Expression Genes Genetic Genetic Transcription Goals Half-Life Health Heart Hour Human Hypothalamic structure Incidence Ion Channel Knowledge Kv channel-interacting protein 2 Label Length Light Long QT Syndrome Mammals Measures Messenger RNA Molecular Molecular Target Mus Myocardial Infarction Patients Pattern Periodicity Persons Phase Phenotype Physiological Potassium Channel Premature Mortality Proteins RNA Regulation Reporter Genes Role Signal Transduction Stroke Sudden Death Telemetry Testing Time Tissues Transcript Transcriptional Regulation Transgenic Mice Uridine cardiovascular risk factor chromatin immunoprecipitation circadian circadian pacemaker heart cell in vivo induced pluripotent stem cell insight mRNA Stability molecular clock mouse model premature promoter shift work suprachiasmatic nucleus transcription factor

项目摘要

Summary Circadian rhythms help to match the optimal function of the cardiovascular system to the daily changes in the environment. Normal cardiovascular rhythms provide a physiological advantage to people. Unfortunately, normal circadian signaling can also unmask a time-of-day pattern in adverse events like heart attack, stroke, and sudden death in patients with underlying cardiovascular disease. Emerging data now show that abnormal or unhealthy daily rhythms can create a negative impact on normal health too. For example shiftwork, which repeatedly causes shifts in endogenous circadian rhythms, is an independent risk factor for cardiovascular disease. In mammals the suprachiasmatic nucleus (SCN) in the brain is the primary circadian pacemaker that helps to entrain endogenous rhythms to the environment. SCN rhythms are synchronized to the environment via light, and its signaling helps to coordinate the molecular rhythms in cells throughout the body. What is new about this application is we determine how repeated changes in light cycle will impact molecular circadian signaling in the heart. Most cells have a molecular clock signaling mechanism that cycles with a periodicity of ~24 hours. We found genetic disruptions in the molecular clock mechanism of heart cells (cardiomyocytes) primarily causes abnormal changes in cardiac electrophysiology by disrupting the regulation of ion channel function. The goal of this application is to determine how repeated shifts in the light cycle impact molecular clock signaling in the mouse heart and its regulation on ion channel function. Aim 1. To identify new mechanisms with which the cardiac molecular clock regulates different ion channels. Aim 2. To determine how repeated changes in light impact molecular clock signaling in the heart and ion channel regulation. This project creates new knowledge at the interface between chronobiology and cardiac electrophysiology.

总结