Malinin G I, Lo H K, Hornicek F J, Malinin T I
Physics Department, Georgetown University, Washington, D.C. 20057.
J Invest Dermatol. 1990 Jul;95(1):97-103. doi: 10.1111/1523-1747.ep12874054.
Ultrastructural alterations of the plasma membrane in HUT 102 lymphoblasts were assessed after a 2-h interaction with a suprapharmacologic (15 micrograms/ml) concentration of 8-MOP, 2-h irradiation with UVA (2.1 mW/cm2), and the exposure of the HUT 102 cells to PUVA under the same conditions. The dark reaction of HUT cells with 8-MOP resulted in the disappearance of microvilli, the emergence of plasma-membrane-associated spherical bodies, formation of lamellar fungiform membrane evaginations, and, in approximately 1% of the cells, formation of uropods and cell capping. Except for uropod formation and cell capping, UVA has induced the same plasma-membrane alterations, and was more deleterious to structural cytoplasmic integrity than 8-MOP. Morphologic changes of the plasma membrane in PUVA-exposed cells tended to replicate structural alterations elicited independently during the dark reaction by suprapharmacologic 8-MOP concentrations. Partial retention of microvilli by cells after PUVA was the sole exception. In light of all available evidence we conclude that psoralen during the dark reactions interacts with plasma membrane lipids by as yet undisclosed mechanisms and that in addition to lipids, membrane proteins are also the primary target of the initial interaction of HUT 102 cells with psoralen during PUVA treatment.
在与超药理浓度(15微克/毫升)的8-甲氧补骨脂素(8-MOP)进行2小时相互作用、用紫外线A(UVA,2.1毫瓦/平方厘米)照射2小时,以及在相同条件下将HUT 102细胞暴露于补骨脂素光化学疗法(PUVA)之后,对HUT 102淋巴母细胞的质膜超微结构改变进行了评估。HUT细胞与8-MOP的暗反应导致微绒毛消失、质膜相关球状体出现、片状菌状膜内陷形成,并且在大约1%的细胞中形成尾足和细胞帽。除了尾足形成和细胞帽形成外,UVA也诱导了相同的质膜改变,并且对细胞质结构完整性的损害比8-MOP更大。暴露于PUVA的细胞中质膜的形态学变化倾向于复制超药理浓度的8-MOP在暗反应期间独立引发的结构改变。PUVA处理后细胞部分保留微绒毛是唯一的例外。根据所有现有证据,我们得出结论,补骨脂素在暗反应期间通过尚未揭示的机制与质膜脂质相互作用,并且除了脂质之外,膜蛋白也是PUVA治疗期间HUT 102细胞与补骨脂素初始相互作用的主要靶点。