在用灰黄霉素短期喂养小鼠后，原卟啉的光毒性与其在小鼠肝脏中的亚细胞定位的关系。
Phototoxicity of protoporphyrin as related to its subcellular localization in mice livers after short-term feeding with griseofulvin.
作者信息
Sandberg S, Romslo I
出版信息
Biochem J. 1981 Jul 15;198(1):67-74. doi: 10.1042/bj1980067.
In mice, feeding with griseofulvin leads to the rapid accumulation of protoporphyrin in liver mitochondria. When liver mitochondria from mice fed with griseofulvin for 2 days are exposed to irradiation (320-400 nm), uncoupling of oxidative phosphorylation followed by inhibition of respiration occurs at light doses above 3-5 kJ/m2. When combined preparations of mitochondria and lysosomes are irradiated, inactivation of enzymes occurs in the following order: succinate dehydrogenase greater than glutamate dehydrogenase greater than acid phosphatase greater than beta-glucuronidase. Qualitatively, the photodamaging effect of endogenously produced protoporphyrin is indistinguishable from that of externally added protoporphyrin. Quantitatively, however, when protoporphyrin is added externally, more protoporphyrin is taken up by lysosomes, and photoinactivation of the lysosomal enzymes is correspondingly more severe. The results are further evidence that porphyrin-induced photodamage is largely determined by the solubility properties of the porphyrins and the target structures [Sandberg & Romslo (1980) Biochim. Biophys. Acta 593, 187-195], and also that protoporphyrin-induced photodamage is essentially similar whether protoporphyrin is generated endogenously or added exogenously.
在小鼠中，用灰黄霉素喂养会导致原卟啉在肝脏线粒体中迅速积累。当用灰黄霉素喂养2天的小鼠的肝脏线粒体受到照射（320 - 400纳米）时，在光剂量高于3 - 5千焦/平方米时，会发生氧化磷酸化解偶联，随后呼吸受到抑制。当线粒体和溶酶体的混合制剂受到照射时，酶的失活按以下顺序发生：琥珀酸脱氢酶＞谷氨酸脱氢酶＞酸性磷酸酶＞β - 葡萄糖醛酸酶。定性地说，内源性产生的原卟啉的光损伤作用与外源性添加的原卟啉的光损伤作用无法区分。然而，定量地说，当外源性添加原卟啉时，溶酶体摄取的原卟啉更多，溶酶体酶的光失活相应更严重。这些结果进一步证明，卟啉诱导的光损伤在很大程度上取决于卟啉的溶解性和靶结构[桑德伯格和罗姆斯洛（1980年）《生物化学与生物物理学报》593，187 - 195]，并且还证明，无论原卟啉是内源性产生还是外源性添加，原卟啉诱导的光损伤基本相似。
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