Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin.

IF 3.5 2区 生物学 Q3 CELL BIOLOGY Molecular and Cellular Biochemistry Pub Date : 2024-12-01 Epub Date: 2024-02-08 DOI:10.1007/s11010-024-04935-z
T A Kavalenia, E A Lapshina, T V Ilyich, Hu-Cheng Zhao, I B Zavodnik
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Abstract

The function of mitochondria as a regulator of myocyte calcium homeostasis has been extensively discussed. The aim of the present work was further clarification of the details of modulation of the functional activity of rat cardiac mitochondria by exogenous Ca2+ ions either in the absence or in the presence of the plant flavonoid naringin. Low free Ca2+ concentrations (40-250 nM) effectively inhibited the respiratory activity of heart mitochondria, remaining unaffected the efficacy of oxygen consumption. In the presence of high exogenous Ca2+ ion concentrations (Ca2+ free was 550 µM), we observed a dramatic increase in mitochondrial heterogeneity in size and electron density, which was related to calcium-induced opening of the mitochondrial permeability transition pores (MPTP) and membrane depolarization (Ca2+free ions were from 150 to 750 µM). Naringin partially prevented Ca2+-induced cardiac mitochondrial morphological transformations (200 µM) and dose-dependently inhibited the respiratory activity of mitochondria (10-75 µM) in the absence or in the presence of calcium ions. Our data suggest that naringin (75 µM) promoted membrane potential dissipation, diminishing the potential-dependent accumulation of calcium ions by mitochondria and inhibiting calcium-induced MPTP formation. The modulating effect of the flavonoid on Ca2+-induced mitochondria alterations may be attributed to the weak-acidic nature of the flavonoid and its protonophoric/ionophoric properties. Our results show that the sensitivity of rat heart mitochondria to Ca2+ ions was much lower in the case of MPTP opening and much higher in the case of respiration inhibition as compared to liver mitochondria.

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钙超载下离体大鼠心脏线粒体的功能活性和形态。柚皮苷的影响
线粒体作为心肌细胞钙稳态调节器的功能已被广泛讨论。本研究的目的是进一步阐明在没有或有植物黄酮柚皮苷的情况下,外源 Ca2+ 离子对大鼠心脏线粒体功能活性的调节细节。低游离 Ca2+ 浓度(40-250 nM)可有效抑制心脏线粒体的呼吸活性,但不影响耗氧量。在外源性 Ca2+ 离子浓度较高(游离 Ca2+ 为 550 µM)的情况下,我们观察到线粒体在大小和电子密度方面的异质性急剧增加,这与钙诱导的线粒体通透性转换孔(MPTP)开放和膜去极化(游离 Ca2+ 离子为 150 至 750 µM)有关。柚皮苷部分阻止了 Ca2+诱导的心脏线粒体形态变化(200 µM),并在无钙离子或有钙离子存在的情况下,剂量依赖性地抑制了线粒体的呼吸活性(10-75 µM)。我们的数据表明,柚皮苷(75 µM)可促进膜电位消散,减少线粒体中钙离子的电位依赖性积累,抑制钙离子诱导的 MPTP 的形成。黄酮类化合物对 Ca2+ 诱导的线粒体变化的调节作用可能归因于黄酮类化合物的弱酸性及其质子/离子特性。我们的研究结果表明,与肝脏线粒体相比,大鼠心脏线粒体对 Ca2+ 离子的敏感性在 MPTP 开放的情况下要低得多,而在呼吸抑制的情况下要高得多。
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来源期刊
Molecular and Cellular Biochemistry
Molecular and Cellular Biochemistry 生物-细胞生物学
CiteScore
8.30
自引率
2.30%
发文量
293
审稿时长
1.7 months
期刊介绍: Molecular and Cellular Biochemistry: An International Journal for Chemical Biology in Health and Disease publishes original research papers and short communications in all areas of the biochemical sciences, emphasizing novel findings relevant to the biochemical basis of cellular function and disease processes, as well as the mechanics of action of hormones and chemical agents. Coverage includes membrane transport, receptor mechanism, immune response, secretory processes, and cytoskeletal function, as well as biochemical structure-function relationships in the cell. In addition to the reports of original research, the journal publishes state of the art reviews. Specific subjects covered by Molecular and Cellular Biochemistry include cellular metabolism, cellular pathophysiology, enzymology, ion transport, lipid biochemistry, membrane biochemistry, molecular biology, nuclear structure and function, and protein chemistry.
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Retraction Note: MiR-146a negatively regulates neutrophil elastase-induced MUC5AC secretion from 16HBE human bronchial epithelial cells. Retraction Note: Topical application of aminopeptidase N-neutralizing antibody accelerates wound closure. Correction to: Mitochondrial complex-1 as a therapeutic target for cardiac diseases. RETRACTED ARTICLE: Upregulation of MCL-1 by LUCAT1 through interacting with SRSF1 promotes the migration and invasion in non-small cell lung carcinoma. Functional activity and morphology of isolated rat cardiac mitochondria under calcium overload. Effect of naringin.
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