Zavodnik I B, Kovalenia T A, Veiko A G, Lapshina E A, Ilyich T V, Kravchuk R I, Zavodnik L B, Klimovich I I
Department of Biochemistry, Yanka Kupala State University of Grodno, Grodno, Belarus.
Grodno State Medical University, Grodno, Belarus.
Biomed Khim. 2022 Aug;68(4):237-249. doi: 10.18097/PBMC20226804237.
The aim of the present work was to elucidate the mechanisms of calcium ion-induced impairments of the ultrastructure and functional activity of isolated rat liver mitochondria in the absence and presence of a number of flavonoids in vitro. In the presence of exogenous Ca²⁺ (20-60 μM), mitochondrial heterogeneity in size and electron density markedly increased: most organelles demonstrated a swollen electron-light matrix, bigger size, elongated cristae and a reduced their number, a damaged native structure of the inner membrane up to its detachment, and some mitochondria showed a more electron-dense matrix (condensed mitochondria). The calcium-induced opening of the mitochondrial permeability transition pores (MPTP) resulted in the ultrastructural disturbances and in the effective inhibition of the respiratory activity of rat liver mitochondria. The flavonoids (10-25 μM) naringenin and catechin, dose-dependently inhibited the respiratory activity of mitochondria and stimulated the MPTP opening in the presence of Ca²⁺ ions. Since Ruthenium red, an inhibitor of the mitochondrial Ca²⁺ uniporter, effectively prevented Ca²⁺-induced MPTP opening both in the absence and presence of flavonoids, we hypothesized that the effect of flavonoids on the MPTP opening could be mediated by stimulation of the Ca²⁺ uniporter.
本研究的目的是阐明在体外不存在和存在多种黄酮类化合物的情况下,钙离子诱导的离体大鼠肝线粒体超微结构和功能活性损伤的机制。在外源Ca²⁺(20 - 60 μM)存在的情况下,线粒体在大小和电子密度上的异质性显著增加:大多数细胞器表现出电子密度低的肿胀基质、更大的尺寸、拉长的嵴且数量减少、内膜原生结构受损直至分离,一些线粒体表现出电子密度更高的基质(浓缩线粒体)。钙诱导的线粒体通透性转换孔(MPTP)开放导致超微结构紊乱,并有效抑制大鼠肝线粒体的呼吸活性。黄酮类化合物(10 - 25 μM)柚皮素和儿茶素在Ca²⁺离子存在的情况下剂量依赖性地抑制线粒体的呼吸活性并刺激MPTP开放。由于线粒体Ca²⁺单向转运体抑制剂钌红在不存在和存在黄酮类化合物的情况下均能有效阻止Ca²⁺诱导的MPTP开放,我们推测黄酮类化合物对MPTP开放的影响可能是通过刺激Ca²⁺单向转运体介导的。