Mitochondrial effects of triarylmethane dyes
Mitochondrial effects of triarylmethane dyes
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DOI：
10.1023/a:1005421112345
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发表时间：
1999-12-01
影响因子：
3
通讯作者：
Vercesi, AE
中科院分区：
文献类型：
--
作者：
Kowaltowski, AJ;Turin, J;Vercesi, AE
研究了亚微摩尔浓度的六种三芳基甲烷染料对线粒体的影响，以及它们在抗氧化光动力治疗中的潜在应用。所有染料都以光动力刺激的方式促进了谷氨酸或琥珀酸支持的非偶联线粒体呼吸的抑制。未观察到N，N，N‘，N’-四甲基-对苯二胺（TMPD）支持呼吸的抑制作用，表明这些染料不影响线粒体复合体IV。当线粒体在没有解偶联剂的情况下被TMPD激活时，用维多利亚蓝R、B或BO处理，促进了线粒体膜电位的耗散和呼吸速率的增加，与线粒体解偶联相一致。即使在黑暗中也能观察到这种作用，EGTA、Mg2+或环孢素A也不能阻止这种作用，这表明染料直接影响线粒体内膜对质子的通透性，从而促进了这种作用。事实上，维多利亚蓝R， B和BO促进了在低氧K+-醋酸盐培养基中培养的缬霉素处理的线粒体的肿胀，证实了这些染料作为经典的质子载体，如FCCP。另一方面，乙基紫、结晶紫和孔孔石绿促进线粒体膜电位耗散，并伴有线粒体肿胀，而EGTA、Mg2+和环孢素a可阻止这一现象，说明这些药物可诱导线粒体通透性转变。线粒体通透化之后是由于细胞色素c释放引起的呼吸抑制，这是由这些药物促进NAD(P)H氧化引起的。
The mitochondrial effects of submicromolar concentrations of six triarylmethane dyes, with potential applications in antioncotic photodynamic therapy, were studied. All dyes promoted an inhibition of glutamate or succinate-supported respiration in uncoupled mitochondria, in a manner stimulated photodynamically. No inhibition of N,N,N',N'-tetramethyl-p-phenylenediamine (TMPD) supported respiration was observed, indicating that these dyes do not affect mitochondrial complex IV. When mitochondria were energized with TMPD in the absence of an uncoupler, treatment with victoria blue R, B, or BO, promoted a dissipation of mitochondrial membrane potential and increase of respiratory rates, compatible with mitochondrial uncoupling. This effect was observed even in the dark, and was not prevented by EGTA, Mg2+ or cyclosporin A, suggesting that it is promoted by a direct effect of the dye on inner mitochondrial membrane permeability to protons. Indeed, victoria blue R, B, and BO promoted swelling of valinomycin-treated mitochondria incubated in a hyposmotic K+-acetate-based medium, confirming that these dyes act as classic protonophores such as FCCP. On the other hand, ethyl violet, crystal violet, and malachite green promoted a dissipation of mitochondrial membrane potential, accompanied by mitochondrial swelling, which was prevented by EGTA, Mg2+, and cyclosporin A, demonstrating that these drugs induce mitochondrial permeability transition. This mitochondrial permeabilization was followed by respiratory inhibition, attributable to cytochrome c release, and was caused by the oxidation of NAD(P)H promoted by these drugs.