• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The Journal of Nutritional Biochemistry >Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction
【24h】

Effect of excess iron on oxidative stress and gluconeogenesis through hepcidin during mitochondrial dysfunction

机译：过量铁对线粒体功能障碍中铁调素通过氧化铁蛋白的氧化应激和糖异生的影响

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Excessive tissue iron levels are a risk factor for insulin resistance and type 2 diabetes, which are associated with alterations in iron metabolism. However, the mechanisms underlying this association are not well understood. This study used human liver SK-HEP-1 cells to examine how excess iron induces mitochondrial dysfunction and how hepcidin controls gluconeogenesis. Excess levels of reactive oxygen species (ROS) and accumulated iron due to iron overload induced mitochondrial dysfunction, leading to a decrease in cellular adenosine triphosphate content and cytochrome c oxidase III expression, with an associated increase in gluconeogenesis. Disturbances in mitochondrial function caused excess iron deposition and unbalanced expression of iron metabolism-related proteins such as hepcidin, ferritin H and ferroportin during the activation of p38 mitogen-activated protein kinase (MAPK) and CCAAT/enhancer-binding protein alpha (C/EBP alpha), which are responsible for increased phosphoenolpyruvate carboxykinase expression. Desferoxamine and n-acetylcysteine ameliorated these deteriorations by inhibiting p38 MAPK and C/EBP alpha activity through iron chelation and ROS scavenging activity. Based on experiments using hepcidin shRNA and hepcidin overexpression, the activation of hepcidin affects ROS generation and iron deposition, which disturbs mitochondrial function and causes an imbalance in iron metabolism and increased gluconeogenesis. Repression of hepcidin activity can reverse these changes. Our results demonstrate that iron overload is associated with mitochondrial dysfunction and that together they can cause abnormal hepatic gluconeogenesis. Hepcidin expression may modulate this disorder by regulating ROS generation and iron deposition. (C) 2015 Elsevier Inc. All rights reserved.
机译：组织中铁水平过高是胰岛素抵抗和2型糖尿病的危险因素，这与铁代谢的改变有关。但是，这种关联的机制尚不十分清楚。这项研究使用人类肝脏SK-HEP-1细胞检查过量的铁如何诱导线粒体功能障碍以及铁调素如何控制糖异生。由于铁超载导致线粒体功能异常，导致过量的活性氧（ROS）和累积的铁水平，导致细胞内三磷酸腺苷含量和细胞色素c氧化酶III表达降低，并伴有糖异生。 p38丝裂原活化蛋白激酶（MAPK）和CCAAT /增强子结合蛋白α（C / EBP）激活期间，线粒体功能紊乱导致铁沉积过多和铁代谢相关蛋白（例如铁调素，铁蛋白H和铁转运蛋白）的表达失衡α），负责增加磷酸烯醇丙酮酸羧激酶的表达。去铁胺和正乙酰半胱氨酸通过铁螯合和ROS清除活性抑制p38 MAPK和C / EBPα活性，从而减轻了这些恶化。基于使用hepcidin shRNA和hepcidin过表达的实验，hepcidin的激活会影响ROS的产生和铁沉积，从而干扰线粒体功能并导致铁代谢失衡和糖异生增加。抑制铁调素活性可以逆转这些变化。我们的结果表明，铁超负荷与线粒体功能障碍有关，并且它们一起可引起异常的肝糖异生。铁调素的表达可能通过调节ROS的产生和铁沉积来调节这种疾病。 （C）2015 Elsevier Inc.保留所有权利。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号