TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis
TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis
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DOI：
10.1016/j.bbrc.2008.11.141
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发表时间：
2009-01-30
影响因子：
3.1
通讯作者：
Araki, Eiichi
中科院分区：
文献类型：
--
作者：
Fujisawa, Kazuo;Nishikawa, Takeshi;Araki, Eiichi
尽管已有报道称，噻唑烷二酮类药物(TZDS)可以减少2型糖尿病患者的心血管事件，但其确切机制尚不清楚。我们先前已经证明，高血糖诱导的线粒体产生的活性氧物种(MtROS)参与了糖尿病并发症的发生，而二甲双胍通过诱导MnSOD的产生和通过激活PGC-1α途径促进线粒体的生物发生而使mt ROS的产生正常化。在这项研究中，我们研究了TZDS是否可以通过激活PGC-1α来抑制高血糖诱导的mtROS的产生。路径。我们发现，吡格列酮和西格列酮可减轻高血糖诱导的人脐静脉内皮细胞(HUVECs)ROS的产生。两种TZD均能增加NRF-1、TFAM和MnSODmRNA的表达。此外，吡格列酮还能增加线粒体DNA和线粒体密度。这些结果表明，TZDS通过诱导MnSOD的产生和通过激活PGC-1α促进线粒体的生物发生来正常化高血糖诱导的mtROS的产生。这一现象可能有助于预防糖尿病血管并发症。(C)2008 Elsevier Inc.保留所有权利。
Although it has been reported that thiazolidinediones (TZDs) may reduce cardiovascular events in type 2 diabetic patients, its precise mechanism is unclear. We previously demonstrated that hyperglycemia-induced production of reactive oxygen species from mitochondria (mtROS) contributed to the development of diabetic complications, and metformin normalized mt ROS production by induction of MnSOD and promotion of mitochondrial biogenesis by activating the PGC-1 alpha pathway. In this study, we examined whether TZDs could inhibit hyperglycemia-induced mtROS production by activating the PGC-1 alpha. pathway. We revealed that pioglitazone and ciglitazone attenuated hyperglycemia-induced ROS production in human umbilical vein endothelial cells (HUVECs). Both TZDs increased the expression of NRF-1, TFAM and MnSOD mRNA. Moreover, pioglitazone increased mtDNA and mitochondrial density. These results suggest that TZDs normalize hyperglycemia-induced mtROS production by induction of MnSOD and promotion of mitochondrial biogenesis by activating PGC-1 alpha. This phenomenon could contribute to the prevention of diabetic vascular complications. (C) 2008 Elsevier Inc. All rights reserved.