Photosensitizing effects of Photofrin II on the site-selected mitochondrial enzymes adenylate kinase and monoamine oxidase.
Photosensitizing effects of Photofrin II on the site-selected mitochondrial enzymes adenylate kinase and monoamine oxidase.
复制标题
DOI：
--
复制
发表时间：
1987-08
期刊：
影响因子：
11.2
通讯作者：
R. S. Murant;S. Gibson;R. Hilf
中科院分区：
文献类型：
--
作者：
R. S. Murant;S. Gibson;R. Hilf
研究了Photofrin II诱导的光敏反应对线粒体单胺氧化酶(MAO)和腺苷酸激酶(AK)活性的影响，以期进一步了解光敏效应的部位特异性。在体外利用完整的线粒体，位于线粒体膜外细胞质一侧的MAO和位于膜间隙的AK均被Photofrin II加光照射所抑制；抑制作用具有药物剂量和光剂量依赖性。当Photofrin II浓度为35微克/ml，剂量为160J/cm2时，MAO活性下降80%，AK活性下降30%。更高剂量的Photofrin II对AK活性没有进一步的影响。AK在不同线粒体制剂中的光敏化研究表明，只有当含有隔离的卟啉的线粒体膜存在于反应混合物中时，AK的活性才会受到明显的抑制。采用体内-体外实验方法，在给药后2~72h取材，药物处理后2 h可见MAO的光敏化(抑制30%)，但随后未观察到活性抑制。AK活性在整个时间过程中没有变化。与位于线粒体膜内膜的细胞色素c氧化酶相比，我们认为在通常的光动力治疗条件下，MAO或AK活性的抑制可能不是肿瘤细胞毒性的原因。
The response to Photofrin II-induced photosensitization on the activities of mitochondrial monoamine oxidase (MAO) and adenylate kinase (AK) were studied in order to gain further insight into site specific effects. Utilizing intact mitochondria in vitro, both MAO, located on the cytoplasmic side of the outer mitochondrial membrane, and AK, located in the intermembrane space, were inhibited by exposure to Photofrin II plus light; inhibition was drug-dose and light-dose dependent. However, MAO activity was inhibited to a greater extent than AK; at 35 micrograms/ml of Photofrin II and 160 J/cm2, MAO activity was decreased by 80% whereas AK activity was inhibited by 30%. Higher doses of Photofrin II had no further effect on AK activity. Studies of photosensitization of AK in different mitochondrial preparations demonstrated that inhibition of activity was evident only when mitochondrial membranes containing sequestered porphyrins were present in the reaction mixture. Using an in vivo-in vitro protocol and sampling at 2 to 72 h after administration of 25 mg/kg of Photofrin II, photosensitization of MAO (30% inhibition) was seen at 2 h after drug treatment but inhibition of activity was not observed at later times. AK activity was unchanged over the entire time course. Compared to cytochrome c oxidase, located in the inner mitochondrial membrane and which displayed a sustained inhibition of activity, we suggest that inhibition of MAO or AK activities probably does not contribute to the tumor cytotoxicity under the usual conditions used for photodynamic therapy.