Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling.
Protective effects of Acyl-coA thioesterase 1 on diabetic heart via PPARα/PGC1α signaling.
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通过PPARα/PGC1α信号传导，酰基辅酶A硫酯酶1对糖尿病心脏的保护作用。
DOI：
10.1371/journal.pone.0050376
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang DW
中科院分区：
文献类型：
--
作者：
Yang S;Chen C;Wang H;Rao X;Wang F;Duan Q;Chen F;Long G;Gong W;Zou MH;Wang DW
据报道，仅使用脂肪酸（FA）生成ATP有助于糖尿病心肌病的发展。本研究旨在探讨底物代谢相关基因在糖尿病心肌病中的作用，为糖尿病心肌病的治疗寻找新的靶点。通过微阵列分析代谢基因表达，酰基辅酶A硫酯酶1（acot 1）在db/db小鼠心肌中明显上调，与正常对照C57 BL/Ks。因此，在db/db小鼠中采用功能获得和功能丧失方法来研究ACOT 1在氧化应激、线粒体功能障碍和心脏功能中的功能。我们发现，在db/db小鼠心脏过表达ACOT 1，H2 O2和丙二醛（MDA）减少，在线粒体ATP酶的活性与线粒体功能的促进，解偶联蛋白3（UCP 3）的表达有助于氧消耗非收缩目的减少，心功能不全减轻，由血流动力学和超声心动图检测。结论ACOT 1缺乏可加速糖尿病引起的心脏损害。值得注意的是，通过实时PCR，我们发现ACOT 1在糖尿病心脏中的过表达抑制了过氧化物酶体增殖物激活受体α/过氧化物酶体增殖物激活受体γ共激活因子1α（PPARα/PGC 1 α）信号传导，表现为PGC 1 α和参与FA使用的下游基因的表达减少。我们的研究结果表明ACOT 1通过PPARα/PGC 1 α信号通路在糖尿病心脏中发挥重要的保护作用。
Using fatty acids (FAs) exclusively for ATP generation was reported to contribute to the development of diabetic cardiomyopathy. We studied the role of substrate metabolism related genes in the heart of the diabetes to find out a novel therapeutic target for diabetic cardiomyopathy. By microarray analysis of metabolic gene expression, acyl-CoA thioesterase 1 (acot1) was clearly upregulated in the myocardia of db/db mice, compared with normal control C57BL/Ks. Therefore, gain-of-function and loss-of-function approaches were employed in db/db mice to investigate the functions of ACOT1 in oxidative stress, mitochondrial dysfunction and heart function. We found that in the hearts of db/db mice which overexpressed ACOT1, H2O2 and malondialdehyde (MDA) were reduced, the activities of ATPases in mitochondria associated with mitochondrial function were promoted, the expression of uncoupling protein 3 (UCP3) contributing to oxygen wastage for noncontractile purposes was decreased, and cardiac dysfunction was attenuated, as determined by both hemodynamic and echocardiographic detections. Consistently, ACOT1 deficiency had opposite effects, which accelerated the cardiac damage induced by diabetes. Notably, by real-time PCR, we found that overexpression of ACOT1 in diabetic heart repressed the peroxisome proliferator-activated receptor alpha/PPARγ coactivator 1α (PPARα/PGC1α) signaling, as shown by decreased expression of PGC1α and the downstream genes involved in FAs use. Our results demonstrated that ACOT1 played a crucial protective role in diabetic heart via PPARα/PGC1α signaling.
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影响因子：
16.2
作者：
Bertoni, AG;Tsai, A;Brancati, FL
通讯作者：
Brancati, FL
影响因子：
15.9
作者：
Finck, BN;Lehman, JJ;Kelly, DP
通讯作者：
Kelly, DP
DOI：
10.1152/ajpheart.01344.2005
发表时间：
2006-06-01
影响因子：
4.8
作者：
Durgan, David J.;Smith, Justin K.;Young, Martin E.
通讯作者：
Young, Martin E.
影响因子：
6.5
作者：
Hunt, MC;Yamada, J;Alexson, SEH
通讯作者：
Alexson, SEH
影响因子：
8.2
作者：
Boudina, Sihem;Abel, Evan Dale
通讯作者：
Abel, Evan Dale