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Protection effect of nicotinamide on cardiomyoblast hypoxia/re-oxygenation injury: study of cellular mitochondrial metabolism

机译:烟酰胺对心肌细胞缺氧/复氧损伤的保护作用:细胞线粒体代谢的研究

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摘要

Hypoxia/re-oxygenation (H/R) injury is an important cause of heart failure and results in a critical metabolism dysfunction. In this paper, the cytoprotective effect of the nicotinamide adenine dinucleotide (NAD) precursor nicotinamide was evaluated using an in vitro model of cardiac H/R injury. Nicotinamide (0-20 mM) was applied to the myoblast cell line H9c2 which was subjected to hypoxia (12, 24, 36 h) followed by a re-oxygenation process (0, 4, 8, 12 h). Cell viability was measured, and mitochondrial metabolites were extracted and then measured by HPLC/MS/MS. The present study showed that nicotinamide could down-regulate the NADH/NAD ratio and then maintain the NAD-dependent metabolism processes. Furthermore, an aberrant decrease of fumarate levels and an increase of succinate levels were observed in the nicotinamide group, which was demonstrated to be caused by nicotinamide-induced succinate dehydrogenase (SDH) inhibition. These results suggest that nicotinamide exerts a protective effect on cardiomyoblasts against H/R-induced injury through both NADH/NAD regulation and reduction of reactive oxygen species generation via SDH inhibition.
机译:缺氧/复氧(H / R)损伤是心力衰竭的重要原因,并导致严重的代谢功能障碍。在本文中,使用心脏H / R损伤的体外模型评估了烟酰胺腺嘌呤二核苷酸(NAD)前体烟酰胺的细胞保护作用。将烟酰胺(0-20 mM)应用于成肌细胞H9c2细胞,使其经受缺氧(12、24、36 h),然后再充氧(0、4、8、12 h)。测量细胞活力,提取线粒体代谢物,然后通过HPLC / MS / MS测量。本研究表明烟酰胺可以下调NADH / NAD比例,然后维持NAD依赖的代谢过程。此外,在烟酰胺组中观察到了富马酸酯水平的异常降低和琥珀酸酯水平的升高,这被证明是由烟酰胺诱导的琥珀酸脱氢酶(SDH)抑制引起的。这些结果表明烟酰胺通过NADH / NAD调节和通过SDH抑制减少活性氧的产生,对心肌母细胞产生抗H / R诱导的损伤的保护作用。

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  • 来源
    《Molecular BioSystems》 |2016年第7期|2257-2264|共8页
  • 作者单位

    Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China;

    Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China;

    Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China;

    Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China;

    Beijing Key Lab of Microanalytical Methods & Instrumentation, Key lab of Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing 100084, P. R. China;

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