Emerging role of heme and heme degradation products in the modulation of cardiac ion channels

血红素和血红素降解产物在心脏离子通道调节中的新作用

基本信息

批准号：
10090373
负责人：
Nirakar Sahoo
金额：
$ 14.8万
依托单位：
UNIVERSITY OF TEXAS RIO GRANDE VALLEY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-09-23 至 2024-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10090373
关键词：
Acute Address Autophagocytosis Biliverdine Binding Biological Assay Calcium-Activated Potassium Channel Carbon Monoxide Cardiac Cardiovascular Diseases Cardiovascular Physiology Cardiovascular system Cause of Death Cell membrane Cells Cessation of life Cysteine Cytochromes Data Deletion Mutagenesis Economic Burden Electrophysiology (science)Environment Ethers Excision Funding Gases Genes Goals Heme Heme Iron Hemin Hemoglobin Hemp Hispanics Histidine Human Imaging Techniques Immunohistochemistry Intake Ion Channel Ion Channel Protein Iron Knowledge Ligation Link Lysosomes Meat Minority-Serving Institution Mitochondria Molecular Mutagenesis Myoglobin Outcomes Research Oxygenases Physiological Play Potassium Channel Process Proteins Protoporphyrins Regulation Reporting Research Role Signal Transduction Signaling Molecule Soluble Guanylate Cyclase System Testing United States Work base cardiovascular disorder risk cofactor experimental study health economics insight iron protoporphyrin IX large-conductance calcium-activated potassium channels mutant non-genomic patch clamp porphyrin a red meat consumption voltage

项目摘要

PROJECT SUMMARY/ABSTRACT Over the past years, research from around the globe has focused on the consumption of red meat and the risk of cardiovascular disease. This positive correlation has been linked to excess heme and its degradation product iron (Fe2+), which are abundant in red meat. Heme serves as a stable cofactor consisting of an iron (Fe2+) coordinated to a porphyrin-IX, often conferring gas sensitivity as exemplified in cytochromes, hemoglobin, myoglobin, and soluble guanylyl cyclase. Excess heme in the system is catabolized by heme oxygenase, which produces carbon monoxide (CO), iron and biliverdin. Emerging evidence, however, suggests a new paradigm of the heme function; intracellular free heme can act as a potent non-genomic acute signaling molecule capable of directly regulating ion channel proteins. Despite the probable physiological and pathophysiological role of heme and other hemp-derived molecules, our knowledge of the acute targets/effectors of heme signaling in the cardiovascular system is severely limited. The goal of this proposal is to define the impacts of heme and heme degradation products (CO) on cardiovascular function by addressing the following questions 1) How do heme and CO impact cardiac ion channels? 2) Does excess heme and CO alter mitophagy in cardiac cells?

项目概要/摘要在过去的几年里，全球各地的研究都集中在红肉的消费及其风险上。心血管疾病。这种正相关性与过量的血红素及其降解有关产品铁（Fe2+），红肉中含量丰富。血红素是一种稳定的辅助因子，由铁组成 (Fe2+) 与卟啉-IX 配位，通常赋予气体敏感性，如细胞色素所示，血红蛋白、肌红蛋白和可溶性鸟苷酸环化酶。系统中多余的血红素被血红素分解代谢加氧酶，产生一氧化碳 (CO)、铁和胆绿素。然而，新出现的证据表明，提出了血红素功能的新范例；细胞内游离血红素可以作为一种有效的非基因组急性物质能够直接调节离子通道蛋白的信号分子。尽管可能存在生理和血红素和其他大麻衍生分子的病理生理作用，我们对急性疾病的了解心血管系统中血红素信号传导的目标/效应器受到严重限制。该提案的目标是通过解决血红素和血红素降解产物 (CO) 对心血管功能的影响以下问题 1) 血红素和 CO 如何影响心脏离子通道？ 2) 血红素和CO是否过量改变心肌细胞的线粒体自噬？