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首页> 外文期刊>Biochimica et biophysica acta. Molecular basis of disease: BBA >Role of sphingomyelinase in mitochondrial ceramide accumulation during reperfusion
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Role of sphingomyelinase in mitochondrial ceramide accumulation during reperfusion

机译:鞘磷脂酶在再灌注过程中在线粒体神经酰胺蓄积中的作用

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摘要

Ceramide accumulation in mitochondria has been associated with reperfusion damage, but the underlying mechanisms are not clearly elucidated. In this work we investigate the role of sphingomyelinases in mitochondrial ceramide accumulation, its effect on reactive oxygen species production, as well as on mitochondrial function by using the sphingomyelinase inhibitor, tricyclodecan-9-yl-xanthogenate (D609). Correlation between neutral sphingomyelinase (nSMase) activity and changes in ceramide content were performed in whole tissue and in isolated mitochondria from reperfused hearts. Overall results demonstrated that D609 treatment attenuates cardiac dysfuncion, mitochondrial injury and oxidative stress. Ceramide was accumulated in mitochondria, but not in the microsomal fraction of the ischemic-reperfused (I/R) group. In close association, the activity of nSMase increased, whereas glutathione (GSH) levels diminished in mitochondria after reperfusion. On the other hand, reduction of ceramide levels in mitochondria from I/R + D609 hearts correlated with diminished nSMase activity, coupling of oxidative phosphorylation and with mitochondrial integrity maintenance. These results suggest that mitochondrial nSMase activity contributes to compartmentation and further accumulation of ceramide in mitochondria, deregulating their function during reperfusion. (C) 2016 Elsevier B.V. All rights reserved.
机译:神经酰胺在线粒体中的积累与再灌注损伤有关,但尚不清楚其潜在机制。在这项工作中,我们研究了鞘磷脂酶在线粒体神经酰胺积聚中的作用,其对活性氧产生的影响以及通过使用鞘磷脂酶抑制剂三环十二烷-9-基-黄原酸酯(D609)对线粒体功能的影响。在整个组织和来自再灌注心脏的分离的线粒体中进行中性鞘磷脂酶(nSMase)活性与神经酰胺含量变化之间的相关性。总体结果表明,D609治疗可减轻心脏功能障碍,线粒体损伤和氧化应激。神经酰胺积聚在线粒体中,但不在缺血再灌注(I / R)组的微粒体部分中积聚。紧密联系在一起,nSMase的活性增加,而再灌注后线粒体中的谷胱甘肽(GSH)水平降低。另一方面,I / R + D609心脏线粒体中神经酰胺水平的降低与nSMase活性降低,氧化磷酸化偶联以及线粒体完整性维持相关。这些结果表明线粒体nSMase活性有助于线粒体内神经酰胺的分隔和进一步积累,从而在再灌注过程中使它们的功能失控。 (C)2016 Elsevier B.V.保留所有权利。

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