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

• 批准号: 10668491
• 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
• 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/10668491
• 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; Health; Heme; Hemin; Hemoglobin; Hemp; Hispanic; 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; Probability; Process; Proteins; Protoporphyrins; Regulation; Reporting; Research; Role; Signal Transduction; Signaling Molecule; Soluble Guanylate Cyclase; System; Testing; Transfection; United States; Work; cardiovascular disorder risk; cofactor; experimental study; insight; iron protoporphyrin IX; large-conductance calcium-activated potassium channels; mutant; non-genomic; patch clamp; porphyrin a; red meat consumption; voltage

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？

项目成果

Analysis of Sanitizer Rotation on the Susceptibility, Biofilm Forming Ability and Caco-2 Cell Adhesion and Invasion of Listeria.

• DOI: 10.3390/pathogens11090961
• 发表时间: 2022-08-24
• 期刊: Pathogens (Basel, Switzerland)
• 作者: Rahman MA;Sahoo N;Yemmireddy V
• 通讯作者: Yemmireddy V

Mechanistic insight into functionally different human islet polypeptide (hIAPP) amyloid: the intrinsic role of the C-terminal structural motifs.

对功能不同的人胰岛多肽 (hIAPP) 淀粉样蛋白的机制洞察：C 端结构基序的内在作用。

• DOI: 10.1039/d2cp01650h
• 发表时间: 2022
• 期刊: Physical chemistry chemical physics : PCCP
• 作者: Sarkar,Dibakar;Maity,NarayanChandra;Shome,Gourav;Varnava,KyriakosGabriel;Sarojini,Vijayalekshmi;Vivekanandan,Subramanian;Sahoo,Nirakar;Kumar,Sourav;Mandal,AtinKumar;Biswas,Ranjit;Bhunia,Anirban
• 通讯作者: Bhunia,Anirban

A rationally designed synthetic antimicrobial peptide against Pseudomonas-associated corneal keratitis: Structure-function correlation.

• DOI: 10.1016/j.bpc.2022.106802
• 发表时间: 2022-07
• 期刊: BIOPHYSICAL CHEMISTRY
• 影响因子: 3.8
• 作者: Mohid, Sk Abdul;Sharma, Prerana;Alghalayini, Amani;Saini, Tripti;Datta, Debarun;Willcox, Mark D. P.;Ali, Haydar;Raha, Sreyan;Singha, Achintya;Lee, DongKuk;Sahoo, Nirakar;Cranfield, Charles G.;Roy, Sanhita;Bhunia, Anirban
• 通讯作者: Bhunia, Anirban