Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts
Curcumin prevents methylglyoxal-induced oxidative stress and apoptosis in mouse embryonic stem cells and blastocysts
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DOI：
10.1002/jcp.20408
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发表时间：
2005-12-01
影响因子：
5.6
通讯作者：
Yu, JS
中科院分区：
文献类型：
--
作者：
Hsuuw, YD;Chang, CK;Yu, JS
丙酮醛（MG）是一种活性二羰基化合物，主要由糖酵解中间体内源性产生。糖尿病患者中升高的MG水平被认为有助于糖尿病并发症。MG通过诱导细胞凋亡而具有细胞毒性。姜黄素，姜黄的黄色色素，已知具有抗氧化和抗炎特性。在本研究中，我们研究了姜黄素对ESC-B5细胞与MG孵育引起的凋亡生化事件的影响。姜黄素抑制MG诱导的DNA断裂、caspase-3激活、PARP裂解、线粒体细胞色素c释放和JNK激活。重要的是，姜黄素还抑制了MG刺激的这些细胞中活性氧（ROS）的增加。此外，我们证明了姜黄素阻止MG诱导的小鼠胚泡从怀孕小鼠分离的凋亡。此外，姜黄素显着减少MG介导的损害小鼠桑椹胚胚囊胚发育。结果支持姜黄素通过阻断ROS形成和随后的凋亡生化事件来抑制MG诱导的小鼠ESC-B5细胞和胚泡凋亡的假设。
Methylglyoxal (MG) is a reactive dicarbonyl compound endogenously produced mainly from glycolytic intermediates. Elevated MG levels in diabetes patients are believed to contribute to diabetic complications. MG is cytotoxic through induction of apoptosis. Curcumin, the yellow pigment of Curcuma longa, is known to have antioxidant and anti-inflammatory properties. In the present study, we examined the effect of curcumin on apoptotic biochemical events caused by incubation of ESC-B5 cells with MG. Curcumin inhibited the MG-induced DNA fragmentation, caspase-3 activation, cleavage of PARP, mitochondrial cytochrome c release, and JNK activation. Importantly, curcumin also inhibited the MG-stimulated increase of reactive oxygen species (ROS) in these cells. In addition, we demonstrated that curcumin prevented the MG-induced apoptosis of mouse blastocysts isolated from pregnant mice. Moreover, curcumin significantly reduced the MG-mediated impairment of blastocyst development from mouse morulas. The results support the hypothesis that curcumin inhibits MG-induced apoptosis in mouse ESC-B5 cells and blastocysts by blocking ROS formation and subsequent apoptotic biochemical events.