Modulation of membrane architecture and function by physiologically relevant and toxic ions

生理相关和有毒离子对膜结构和功能的调节

• 批准号: 261700-2012
• 负责人: Prenner, Elmar
• 金额: $ 1.82万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=571121
• 关键词: Modulation; membrane; architecture; function; physiologically

Toxic metals are at the core of significant and growing concerns to the Natural Sciences and Engineering fields in Canada and beyond. Indeed, ion mixtures of toxic metals disrupt physiology via mechanisms that remain poorly understood. In accord with my long term research interest in the structure and function of biomembranes, this proposal addresses the impact of ions and toxic metals on membranes. The impact of essential ions Na+, K+ and Ca++ is compared with the common pollutants Cd++ and Hg++. Ion combinations are important since the human body is exposed to a mix of pollutants which may increase their effects. These ions differ in their toxicity as Cd++ was reported as a problem for wildlife whereas Hg++ is more a concern for domestic animals. Ion-membrane interactions are studied in four areas: i) ion binding to the surface: Using a novel assay we have shown that Hg++ preferred negatively charged phosphatidylserine (PS) whereas Cd++ interacted stronger with zwitterionic phosphatidylethanolamines. ii) impact on membrane dynamics: The interaction of toxic divalent ions often decreased membrane fluidity and increased of membrane permeability which both effect cellular function. A comprehensive analysis in terms of lipid composition and the use of ion mixtures is proposed. iii) impact on membrane organization: Ions can impact the lipid phase behavior and induce clustering of lipids as seen for the interactions of Ca++ and PS whereby resulting patches bind proteins. iv) impact on red blood cells and extracts: Model systems will be compared with biological extracts and blood cells. Changes of the characteristic discoidal shape of red blood cells by Cd++ and Hg++ have been reported but not in a concentration dependant manner or after exposure to ion mixtures. The proposed work is significant as a comprehensive investigation of the impact of ions on biomembranes. A better understanding of the basic biological principles may help to uncover better means to control the effects of pollutants on wildlife, livestock and indeed public health.

有毒金属是加拿大及其他地区自然科学和工程领域日益关注的核心问题。事实上，有毒金属的离子混合物通过仍然知之甚少的机制破坏生理学。雅阁我对生物膜结构和功能的长期研究兴趣，本提案涉及离子和有毒金属对膜的影响。比较了人体必需离子Na+、K+、Ca++与常见污染物Cd++、Hg++的影响。离子组合很重要，因为人体暴露于可能增加其影响的污染物混合物中。这些离子的毒性不同，据报道，Cd++是野生动物的一个问题，而Hg++则是家畜的一个问题。离子-膜相互作用在四个方面进行了研究： i）与表面的离子结合：使用新的测定，我们已经表明Hg++优选带负电荷的磷脂酰丝氨酸（PS），而Cd++与两性离子磷脂酰乙醇胺的相互作用更强。 ii）对膜动力学的影响：有毒二价离子的相互作用通常降低膜流动性并增加膜渗透性，这两者都影响细胞功能。一个全面的分析，在脂质成分和离子混合物的使用提出。 iii）对膜组织的影响：离子可以影响脂质相行为并诱导脂质的聚集，如Ca++和PS的相互作用所见，由此产生的斑块结合蛋白质。 iv）对红细胞和提取物的影响：将模型系统与生物提取物和血细胞进行比较。Cd++和Hg++引起的红细胞盘状形态特征的变化已有报道，但不是以浓度依赖性方式或暴露于离子混合物后发生的。 这项工作对于全面研究离子对生物膜的影响具有重要意义。更好地理解基本的生物学原理可能有助于发现更好的方法来控制污染物对野生动物、牲畜乃至公众健康的影响。