激素通过激活心脏线粒体内膜中对ATP敏感的K+通道来诱导细胞保护
Fikret Er1, Guido Michels, Natig Gassanov
1Department of Internal Medicine III, University of Cologne, Cologne, Germany.
Circulation
|November 3, 2004
概括
激素通过激活线粒体ATP敏感通道 (mitoKATP) 来保护心脏细胞免受损伤. 这一发现表明,丸激素可能有助于心脏病发作后的恢复.
科学领域:
- 心血管科学 心血管科学
- 内分泌学 在内分泌学.
- 细胞生理学 细胞生理学
背景情况:
- 历史上,雄激素与不良的心血管影响有关.
- 新出现的证据表明,丸激素可能有利于心肌缺血/再输后的心肌恢复.
- 对ATP敏感通道在的心脏保护作用中的作用需要阐明.
研究的目的:
- 为了调查丸激素是否能改善心肌缺血的耐受性.
- 为了确定这种效应是由线粒体 (mitoKATP) 或肉质体 (sarcKATP) KATP通道介导的.
主要方法:
- 利用细胞缺血模型来评估心肌细胞死亡.
- 测量了线粒体黄蛋白光度以指数线粒体ATP活性.
- 进行了补丁实验,以评估完整的肌细胞和分离的线粒细胞中的KATP通道功能.
主要成果:
- 丸激素显著降低了因缺血引起的心肌细胞死亡,这种效应被5-基酸 (一种mitoKATP抑制剂) 阻止.
- 丸激素增加了线粒体黄蛋白光,表明线粒体KATP的激活,这是K+依赖和ATP敏感的.
- 在单通道记录中观察到丸激素对线粒体内膜KATP通道的直接激活;没有发现对sarcKATP通道的影响.
结论:
- 提供了对心脏mitoKATP通道的直接证据.
- 建立了激素诱导的细胞保护和mitoKATP通道激活之间的联系.
- 表明内源性丸激素可能在心肌梗塞后的康复中发挥重要作用.
相关概念视频
01:28The Inner Mitochondrial Membrane
The inner mitochondrial membrane is the primary site of ATP synthesis. The inner membrane domain that forms a smooth layer adjacent to the outer membrane is called the inner boundary membrane. This domain contains membrane transporters that drive metabolites in and out of the mitochondria. In contrast, the inner membrane network that invaginates into the matrix space is called the cristae membrane. This domain accounts for principle mitochondrial function as it accommodates the protein...
01:46Electron Transport Chain: Complex I and II
The mitochondrial electron transport chain (ETC) is the main energy generation system in the eukaryotic cells. However, mitochondria also produce cytotoxic reactive oxygen species (ROS) due to the large electron flow during oxidative phosphorylation. While Complex I is one of the primary sources of superoxide radicals, ROS production by Complex II is uncommon and may only be observed in cancer cells with mutated complexes.
ROS generation is regulated and maintained at moderate levels necessary...
ROS generation is regulated and maintained at moderate levels necessary...
01:48ATP Synthase: Mechanism
In animals, the mitochondrial F1F0 ATP synthase is the key protein that synthesizes ATP molecules through a complex catalytic mechanism. While the nuclear genome encodes the majority of ATP synthase subunits, the mitochondrial genome encodes some of the enzyme's most critical components. The formation of this multi-subunit enzyme is a complex multi-step process regulated at the level of transcription, translation, and assembly. Defects in one or more of these steps can result in decreased ATP...
01:39Mitochondrial Protein Sorting
Mitochondria are double-membrane organelles of the eukaryotes involved in cellular metabolism, signaling, ATP synthesis, and programmed cell death. Each of these processes requires specific proteins and enzymes that must be correctly sorted to the right mitochondrial subcompartment for the proper functioning of the organelle.
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
Most of these mitochondrial proteins are encoded by the nucleus and imported to the mitochondria as unfolded or loosely folded precursors. Mitochondrial precursors...
01:19Translocation of Proteins into the Mitochondria
Mitochondrial precursors are translocated to the internal subcompartments via independent mechanisms involving distinct protein machineries called translocases.
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
Sorting of outer membrane proteins:
Mitochondrial outer membrane proteins are of two types: the transmembrane, beta-barrel porins, and the membrane-anchored, alpha-helical proteins. Beta-barrel porin precursors are translocated by the TOM complex and inserted into the outer mitochondrial membrane by the SAM complex. In contrast,...
01:37Energy to Drive Translocation
Mitochondrial protein import is powered by two distinct energy sources: ATP hydrolysis and electrochemical potential across the inner membrane. Newly synthesized precursors are bound by cytosolic chaperones of the Hsp70 family, which guide them to the import receptors on the mitochondrial surface. Utilizing the energy of ATP hydrolysis, Hsp70 chaperones transfer these precursors to the TOM receptors on the mitochondrial outer membrane.
Generally, polypeptides are unfolded by two distinct...
Generally, polypeptides are unfolded by two distinct...