Butylated hydroxytoluene and inorganic phosphate plus Ca2+ increase mitochondrial permeability via mutually exclusive mechanisms
Butylated hydroxytoluene and inorganic phosphate plus Ca2+ increase mitochondrial permeability via mutually exclusive mechanisms
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丁基羟基甲苯和无机磷酸盐加上 Ca2 通过相互排斥的机制增加线粒体通透性
DOI：
--
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发表时间：
1996
影响因子：
3
通讯作者：
Lisa M. Haley
中科院分区：
文献类型：
--
作者：
P. M. Sokolove;Lisa M. Haley
线粒体经历渗透性转变（PT），即对小溶质变得非选择性渗透，以响应广泛的条件/化合物。一般来说，通透性过渡孔（PTP）的打开是Ca2+-和pi依赖的，并被环孢素A （CsA）、三氟拉嗪（TFP）、ADP和丁基羟基甲苯（BHT）阻断。然而，Gudz和同事已经报道[第7届欧洲生物能量学会议，EBEC Short Reports(1992) 7,125]，在某些条件下，BHT通过可能不具有所有这些特征的过程增加线粒体通透性。具体来说，他们确定bht诱导的通透性转变与Ca2+无关，对CsA不敏感。我们使用线粒体肿胀来更详细地比较BHT和Ca2+ + Pi诱导的通透性变化，结果如下。(1)通透性对BHT浓度的依赖是三相的：存在BHT浓度阈值（约60 nmol BHT/ mg线粒体蛋白），低于该阈值不增加；BHT在中等浓度范围内提高渗透率；在高BHT浓度（> - 120 nmol/mg）下，渗透率再次降低。(2) BHT的作用取决于BHT与线粒体蛋白的比例。(3) BHT浓度过低，不能诱导肿胀，可阻断Ca2+和Pi诱导的PT。(4) Ca2+触发PT对Pi浓度的依赖是双相的。低于阈值50-100 ΜM，不发生肿胀。超过这个阈值，肿胀迅速增加。(5) Pi水平过低无法支持Ca2+诱导的PT抑制bht诱导的肿胀。(6)阻断Ca2+ + Pi诱导的PT的药物和治疗可以缓解BHT诱导的肿胀。这些数据表明BHT和Ca2+ + Pi通过两种相互排斥的机制增加线粒体通透性。
Mitochondria undergo a permeability transition (PT), i.e., become nonselectively permeable to small solutes, in response to a wide range of conditions/compounds. In general, opening of the permeability transition pore (PTP) is Ca2+- and Pi-dependent and is blocked by cyclosporin A (CsA), trifluoperazine (TFP), ADP, and butylated hydroxytoluene (BHT). Gudz and coworkers have reported [7th European Bioenergetics Conference, EBEC Short Reports (1992)7, 125], however, that, under some conditions, BHT increases mitochondrial permeability via a process that may not share all of these characteristics. Specifically, they determined that the BHT-induced permeability transition was independent of Ca2+ and was insensitive to CsA. We have used mitochondrial swelling to compare in greater detail the changes in permeability induced by BHT and by Ca2+ plus Pi with the following results. (1) The dependence of permeability on BHT concentration is triphasic: there is a threshold BHT concentration (ca. 60 nmol BHT/ mg mitochondrial protein) below which no increase occurs; BHT enhances permeability in an intermediate concentration range; and at high BHT concentrations (> 120 nmol/mg) permeability is again reduced. (2) The effects of BHT depend on the ratio of BHT to mitochondrial protein. (3) Concentrations of BHT too low to induce swelling block the PT induced by Ca2+ and Pi. (4) The dependence of the Ca2+-triggered PT on Pi concentration is biphasic. Below a threshold of 50–100 ΜM, no swelling occurs. Above this threshold swelling increases rapidly. (5) Pi levels too low to support the Ca2+-induced PT inhibit BHT-induced swelling. (6) Swelling induced by BHT can bestimulated by agents and treatments that block the PT induced by Ca2+ plus Pi. These data suggest that BHT and Ca2+ plus Pi, increase mitochondrial permeability via two mutually exclusive mechanisms.
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DOI：
--
发表时间：
1984
期刊：
The Journal of biological chemistry
影响因子：
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作者：
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Sokolove,PM
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DOI：
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期刊：
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DOI：
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期刊：
Biochimica et biophysica acta
影响因子：
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