• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Myocardial preconditioning signal transduction pathways linking muscarinic receptors to the mitochondrial K(ATP) channel-dependent ROS production in the heart.
【24h】

Myocardial preconditioning signal transduction pathways linking muscarinic receptors to the mitochondrial K(ATP) channel-dependent ROS production in the heart.

机译：心肌预处理信号转导通路，将毒蕈碱受体与心脏中线粒体K（ATP）通道依赖性ROS产生相关联。

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

Ischemic preconditioning (IPC) refers to the phenomenon by which brief episodes of ischemia and reperfusion render the myocardium resistant to necrosis from a subsequent otherwise lethal ischemia. IPC is triggered by receptors. Cardioprotection from acetylcholine (ACh), bradykinin (BK) and opioids is dependent on reactive oxygen species (ROS), which are thought to result from opening of mitochondrial ATP-sensitive potassium channels (mKATP). The aim of this dissertation was to determine the signaling components between cell membrane receptors and opening of mKATP.; Infarct size was measured in buffer-perfused isolated rabbit hearts. Myocardial infarction was induced by 30 min of regional ischemia with reperfusion. IPC was induced by 5 min global ischemia and 10 min reperfusion prior to the 30 min regional ischemia. ROS were measured in isolated adult rabbit cardiomyocytes. Phosphorylation of proteins or cGMP was measured in myocardial biopsies.; Because inhibition of respiratory chain complex III blocked ACh's cardioprotection, while NAD(P)H blockade did not, I conclude that mitochondria are the source of the ROS burst. My studies reveal that ACh requires phosphatidylinositol-3-OH-kinase (PI3-kinase) and at least one tyrosine kinase to trigger the preconditioned state while adenosine (Aden) does not. My experiments also show that the epidermal growth factor receptor (EGFR) is likely to be the site of the tyrosine kinase. In other cell types ACh causes release of HB-EGF by activating a metalloproteinase. As expected a metalloproteinase inhibitor blocked ACh's protection.; My experiments reveal that ACh triggers mKATP opening by activating nitric oxide synthase (NOS). Nitric oxide activates guanylyl cyclase (GC) to generate cGMP, which activates protein kinase G (PKG). ACh's protection was blocked by either L-NIO (a NOS blocker) or 1H-[1, 2, 4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ, a GC blocker). Similarly, cardioprotection from 8-(4-chlorophenylthio) guanosine 3',5' -cyclic monophosphate (8-pCPT-cGMP, a direct activator of PKG) was blocked by a free radical scavenger and an mKATP blocker.; In conclusion, ACh protects the heart by a pathway different from that used by Aden. EGFR, PI3-kinase, NOS, GC, mKATP, and ROS, in that order, are essential signaling components by which ACh triggers preconditioning. Aden bypasses all of the above to protect the heart.
机译：缺血预处理（IPC）是指短暂的局部缺血和再灌注使心肌对继发的致命性局部缺血产生的坏死具有抵抗力的现象。 IPC由受体触发。对乙酰胆碱（ACh），缓激肽（BK）和阿片类药物的心脏保护作用依赖于活性氧（ROS），后者被认为是由于线粒体ATP敏感性钾通道（mKATP）的开放所致。本论文的目的是确定细胞膜受体与mKATP开放之间的信号传导成分。在灌注缓冲液的离体兔心脏中测量梗塞面积。局部缺血30分钟再灌注可诱发心肌梗塞。在30分钟的局部缺血之前，通过5分钟的整体缺血和10分钟的再灌注诱导IPC。在分离的成年兔心肌细胞中测量ROS。在心肌活检中测量蛋白质或cGMP的磷酸化。因为抑制呼吸链复合物III会阻止ACh的心脏保护，而NAD（P）H则没有，我认为线粒体是ROS爆发的来源。我的研究表明，ACh需要磷脂酰肌醇3-OH激酶（PI3-激酶）和至少一种酪氨酸激酶来触发预设状态，而腺苷（Aden）则不需要。我的实验还表明，表皮生长因子受体（EGFR）可能是酪氨酸激酶的位点。在其他细胞类型中，ACh通过激活金属蛋白酶导致HB-EGF释放。如预期的那样，金属蛋白酶抑制剂阻止了ACh的保护。我的实验表明，ACh通过激活一氧化氮合酶（NOS）触发mKATP的开放。一氧化氮激活鸟苷酸环化酶（GC）生成cGMP，后者激活蛋白激酶G（PKG）。 ACh的保护被L-NIO（一种NOS阻断剂）或1H- [1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮（ODQ，一种GC阻断剂）阻断。类似地，通过自由基清除剂和mKATP阻断剂阻断了对8-（4-氯苯硫基）鸟苷3'，5'-环单磷酸酯（8-pCPT-cGMP，PKG的直接活化剂）的心脏保护。总之，ACh通过与Aden不同的途径保护心脏。依此顺序，EGFR，PI3激酶，NOS，GC，mKATP和ROS是ACh触发预处理的重要信号成分。亚丁绕过上述所有事物以保护心脏。

著录项

  • 作者

    Qin, Qining.;

  • 作者单位

    University of South Alabama.;

  • 授予单位 University of South Alabama.;
  • 学科 Health Sciences Pathology.; Biology Animal Physiology.; Biology Cell.
  • 学位 Ph.D.
  • 年度 2004
  • 页码 227 p.
  • 总页数 227
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 病理学;生理学;细胞生物学;
  • 关键词

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