Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes.
Alteration in mitochondrial Ca(2+) uptake disrupts insulin signaling in hypertrophic cardiomyocytes.
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DOI：
10.1186/s12964-014-0068-4
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发表时间：
2014-11-07
期刊：
影响因子：
--
通讯作者：
Lavandero S
中科院分区：
文献类型：
--
作者：
Gutiérrez T;Parra V;Troncoso R;Pennanen C;Contreras-Ferrat A;Vasquez-Trincado C;Morales PE;Lopez-Crisosto C;Sotomayor-Flores C;Chiong M;Rothermel BA;Lavandero S
心脏肥大的特征在于心脏生物能量学和胰岛素敏感性的改变。胰岛素促进心肌细胞摄取葡萄糖，并将其用作糖酵解和线粒体氧化的底物，以维持高的心脏能量需求。胰岛素刺激Ca 2+从内质网释放，然而，这如何转化为健康或肥大心肌细胞中线粒体代谢的变化尚不完全清楚。在本研究中，我们研究了正常和去甲肾上腺素或胰岛素样生长因子-1诱导的肥大心肌细胞中胰岛素依赖的线粒体Ca 2+信号。使用胰岛素选择性Ca 2+荧光探针，我们发现，胰岛素增加线粒体Ca 2+水平。该信号被肌醇1，4，5-三磷酸受体或线粒体Ca 2+单向转运体的药理学阻断以及siRNA依赖性线粒体Ca 2+单向转运体敲低所抑制。去甲肾上腺素刺激的心肌细胞表现出显着减少内质网线粒体接触相比，无论是控制或胰岛素样生长因子-1刺激的细胞。这导致响应于胰岛素的线粒体Ca 2+摄取、Akt活化、葡萄糖摄取和氧消耗减少。阻断线粒体Ca 2+摄取足以模拟去甲肾上腺素诱导的心肌细胞肥大对胰岛素信号传导的影响。线粒体Ca 2+摄取是心肌细胞胰岛素信号转导和代谢的关键事件。本文的在线版本（doi：10.1186/s12964-014-0068-4）包含补充材料，可供授权用户使用。
Cardiac hypertrophy is characterized by alterations in both cardiac bioenergetics and insulin sensitivity. Insulin promotes glucose uptake by cardiomyocytes and its use as a substrate for glycolysis and mitochondrial oxidation in order to maintain the high cardiac energy demands. Insulin stimulates Ca2+ release from the endoplasmic reticulum, however, how this translates to changes in mitochondrial metabolism in either healthy or hypertrophic cardiomyocytes is not fully understood. In the present study we investigated insulin-dependent mitochondrial Ca2+ signaling in normal and norepinephrine or insulin like growth factor–1-induced hypertrophic cardiomyocytes. Using mitochondrion-selective Ca2+-fluorescent probes we showed that insulin increases mitochondrial Ca2+ levels. This signal was inhibited by the pharmacological blockade of either the inositol 1,4,5-triphosphate receptor or the mitochondrial Ca2+ uniporter, as well as by siRNA-dependent mitochondrial Ca2+ uniporter knockdown. Norepinephrine-stimulated cardiomyocytes showed a significant decrease in endoplasmic reticulum-mitochondrial contacts compared to either control or insulin like growth factor–1-stimulated cells. This resulted in a reduction in mitochondrial Ca2+ uptake, Akt activation, glucose uptake and oxygen consumption in response to insulin. Blocking mitochondrial Ca2+ uptake was sufficient to mimic the effect of norepinephrine-induced cardiomyocyte hypertrophy on insulin signaling. Mitochondrial Ca2+ uptake is a key event in insulin signaling and metabolism in cardiomyocytes. The online version of this article (doi:10.1186/s12964-014-0068-4) contains supplementary material, which is available to authorized users.
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影响因子：
64.5
作者：
Cárdenas C;Miller RA;Smith I;Bui T;Molgó J;Müller M;Vais H;Cheung KH;Yang J;Parker I;Thompson CB;Birnbaum MJ;Hallows KR;Foskett JK
通讯作者：
Foskett JK
线粒体网络和内质网之间的结构和功能联系。
DOI：
10.1016/j.biocel.2009.04.010
发表时间：
2009-10
影响因子：
4
作者：
Giorgi, Carlotta;De Stefani, Diego;Bononi, Angela;Rizzuto, Rosario;Pinton, Paolo
通讯作者：
Pinton, Paolo
DOI：
10.1073/pnas.1210718109
发表时间：
2012-08-07
影响因子：
11.1
作者：
Drago, Ilaria;De Stefani, Diego;Pozzan, Tullio
通讯作者：
Pozzan, Tullio
影响因子：
--
作者：
ALLARD, MF;SCHONEKESS, BO;LOPASCHUK, GD
通讯作者：
LOPASCHUK, GD
DOI：
10.1016/0006-291x(63)90377-2
发表时间：
1963-01-01
影响因子：
3.1
作者：
LEHNINGER, AL;GREENAWAY, JW;ROSSI, CS
通讯作者：
ROSSI, CS