Minocycline chelates Ca2+, binds to membranes, and depolarizes mitochondria by formation of Ca2+-dependent ion channels.
Minocycline chelates Ca2+, binds to membranes, and depolarizes mitochondria by formation of Ca2+-dependent ion channels.
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DOI：
10.1007/s10863-010-9271-1
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发表时间：
2010-04
影响因子：
3
通讯作者：
Krasnikov, Boris F.
中科院分区：
文献类型：
--
作者：
Antonenko, Yuri N.;Rokitskaya, Tatyana I.;Cooper, Arthur J. L.;Krasnikov, Boris F.
二甲胺四环素（FDA批准的一种消炎药）已被报道对肌萎缩侧索硬化症和亨廷顿病的小鼠模型有效。有人认为二甲胺四环素的有益作用与其影响线粒体功能的能力有关。我们验证了二甲胺四环素直接抑制Ca2+诱导的大鼠肝脏线粒体通透性转变的假设。我们的数据显示二甲胺四环素不直接抑制线粒体通透性转变。然而，二甲胺四环素对线粒体功能有多重影响。首先，这种药物螯合Ca2+离子。其次，二甲胺四环素以Ca2+依赖的方式与线粒体膜结合。其三，二甲胺四环素通过在线粒体内膜形成离子通道降低质子动力。两个双层脂膜模型证实了通道的形成。我们表明二甲胺四环素，在Ca2+的存在下，诱导小离子的选择性通透性。我们认为米诺环素的有益作用与线粒体的Ca2+依赖性部分解偶联有关，这间接阻止了线粒体通透性转变的诱导。
Minocycline (an anti-inflammatory drug approved by the FDA) has been reported to be effective in mouse models of amyotrophic lateral sclerosis and Huntington disease. It has been suggested that the beneficial effects of minocycline are related to its ability to influence mitochondrial functioning. We tested the hypothesis that minocycline directly inhibits the Ca2+-induced permeability transition in rat liver mitochondria. Our data show that minocycline does not directly inhibit the mitochondrial permeability transition. However, minocycline has multiple effects on mitochondrial functioning. First, this drug chelates Ca2+ ions. Secondly, minocycline, in a Ca2+-dependent manner, binds to mitochondrial membranes. Thirdly, minocycline decreases the proton-motive force by forming ion channels in the inner mitochondrial membrane. Channel formation was confirmed with two bilayer lipid membrane models. We show that minocycline, in the presence of Ca2+, induces selective permeability for small ions. We suggest that the beneficial action of minocycline is related to the Ca2+-dependent partial uncoupling of mitochondria, which indirectly prevents induction of the mitochondrial permeability transition.
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影响因子：
5.4
作者：
Kupsch, Kathleen;Hertel, Silvia;Schoenfeld, Peter
通讯作者：
Schoenfeld, Peter
DOI：
10.1111/j.1749-6632.1994.tb24741.x
发表时间：
1994-01-01
期刊：
INHIBITION OF MATRIX METALLOPROTEINASES: THERAPEUTIC POTENTIAL
影响因子：
--
作者：
SIPOS, EP;TAMARGO, RJ;BREM, H
通讯作者：
BREM, H
DOI：
10.1016/j.bbrc.2003.10.191
发表时间：
2003-12-19
影响因子：
3.1
作者：
Matsuki, S;Iuchi, Y;Fujii, J
通讯作者：
Fujii, J
影响因子：
4.3
作者：
Krasnikov, BF;Zorov, DB;Brown, AM
通讯作者：
Brown, AM
DOI：
10.1073/pnas.0306239101
发表时间：
2004-03-02
影响因子：
11.1
作者：
Teng, YD;Choi, H;Friedlander, RM
通讯作者：
Friedlander, RM