Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes.
Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes.
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DOI：
10.1371/journal.pone.0041663
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Kakkar P
中科院分区：
文献类型：
--
作者：
Kapoor R;Kakkar P
细胞凋亡是糖尿病肝损伤的早期事件，氧化应激与肝细胞凋亡加速有关。因此，能够抑制ROS的化合物可能对高糖诱导的细胞凋亡具有调节作用。在本研究中，原代大鼠肝细胞暴露于高浓度（40 mM）的葡萄糖。在该浓度下，观察到细胞活力降低和ROS生成增强。从抗氧化酶的转录水平和活性来看，高糖胁迫下肝细胞的抗氧化状态也明显下降。此外，线粒体去极化伴随着线粒体完整性的丧失和Bax和Bcl-2表达的改变。还观察到AIF（凋亡诱导因子）和Endo-G（内切核酸酶-G）等凋亡蛋白从其驻留位置线粒体转移到细胞核的增加。位于线粒体膜间隙的Cyt-c也移位到细胞质中。这些凋亡蛋白启动caspase激活，DNA断裂，染色质凝聚，增加凋亡DNA含量在葡萄糖处理的肝细胞，表明线粒体介导的细胞死亡的凋亡模式。桑色素是一种从番石榴中提取的黄酮类化合物，能有效地提高细胞活力和降低ROS水平。它维持线粒体的完整性，抑制线粒体凋亡蛋白的释放，防止DNA断裂，染色质浓缩和亚二倍体DNA暴露于高糖。本研究证实了膳食黄酮桑色素通过干预氧化应激，通过线粒体介导的途径调节高糖诱导的细胞凋亡的能力。
Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM) of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor) & Endo-G (endonuclease-G) from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress.
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影响因子：
10.2
作者：
Barathmanikanth S;Kalishwaralal K;Sriram M;Pandian SR;Youn HS;Eom S;Gurunathan S
通讯作者：
Gurunathan S
DOI：
10.1073/pnas.0914013107
发表时间：
2010-05-18
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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作者：
Kandhare, Amit D.;Raygude, Kiran S.;Bodhankar, Subhash L.
通讯作者：
Bodhankar, Subhash L.
影响因子：
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作者：
Das, Joydeep;Sil, Parames C.
通讯作者：
Sil, Parames C.
DOI：
10.1152/ajpendo.00683.2007
发表时间：
2008-10-01
影响因子：
5.1
作者：
Han, Zhiming;Vassena, Rita;Latham, Keith E.
通讯作者：
Latham, Keith E.