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吩噻嗪衍生物的光毒性。II. 红细胞膜蛋白的光敏交联

Phototoxicity of phenothiazine derivatives. II. Photosensitized cross-linking of erythrocyte membrane proteins.

作者信息

Merville M P, Piette J, Decuyper J, Calberg-Bacq C M, van de Vorst A

出版信息

Chem Biol Interact. 1983 Jun;44(3):275-87. doi: 10.1016/0009-2797(83)90055-8.

DOI:10.1016/0009-2797(83)90055-8
PMID:6872093
Abstract

Irradiation in the presence of O2, with near-UV light of five promazine (PZ) derivatives added to erythrocyte ghost membranes, causes covalent cross-linking between proteins as revealed by a progressive decrease in the amounts of proteins separable by electrophoresis after denaturation. The induction of cross-links in the two spectrin subunits is a single-hit process as a function of the irradiation time; relatively the rate constants (in min-1) of the photoreactions were 0.060 with chlorpromazine (CPZ), 0.039 with methoxypromazine (MTPZ), 0.031 with PZ, 0.029 with triflupromazine (TFPZ) and 0.006 with acepromazine (ACPZ). A main photochemical intermediate implicated in the spectrin aggregation seems to be the cation radical of the PZ derivatives. Indeed, (i) the chemically generated cation radicals can induce the reaction in the dark; (ii) the photoaggregation is regularly reduced upon addition of increasing concentrations of NaN3; (iii) NaN3 similarly affects the amount of cross-links induced by the isolated cation radicals. Hydroxyl radicals are also involved in the photocross-linking when the reaction is initiated only by MTPZ and not by the other sensitizers. In the absence of oxygen during irradiation, PZ, MTPZ and ACPZ completely loose their cross-linking activities whereas CPZ and TFPZ remain as efficient as in the presence of oxygen.

摘要

在向红细胞影膜中添加五种丙嗪(PZ)衍生物的近紫外光照射下,在有氧气存在的情况下,会导致蛋白质之间发生共价交联,这可通过变性后电泳可分离的蛋白质数量逐渐减少来揭示。两个血影蛋白亚基中交联的诱导是一个单 hit 过程,是照射时间的函数;相对而言,光反应的速率常数(以分钟⁻¹ 计),氯丙嗪(CPZ)为 0.060,甲氧丙嗪(MTPZ)为 0.039,PZ 为 0.031,三氟丙嗪(TFPZ)为 0.029,乙酰丙嗪(ACPZ)为 0.006。与血影蛋白聚集有关的主要光化学中间体似乎是 PZ 衍生物的阳离子自由基。实际上,(i)化学产生的阳离子自由基可在黑暗中诱导反应;(ii)随着叠氮化钠浓度的增加,光聚集会有规律地减少;(iii)叠氮化钠同样会影响由分离的阳离子自由基诱导的交联量。当仅由 MTPZ 而非其他敏化剂引发反应时,羟基自由基也参与光交联。在照射期间无氧的情况下,PZ、MTPZ 和 ACPZ 完全丧失其交联活性,而 CPZ 和 TFPZ 仍与有氧气存在时一样有效。

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Phototoxicity of phenothiazine derivatives. II. Photosensitized cross-linking of erythrocyte membrane proteins.吩噻嗪衍生物的光毒性。II. 红细胞膜蛋白的光敏交联
Chem Biol Interact. 1983 Jun;44(3):275-87. doi: 10.1016/0009-2797(83)90055-8.
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引用本文的文献

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Inhibition and Ultraviolet-Induced Chemical Modification of UDP-Glucose:(1,3)-beta-Glucan (Callose) Synthase by Chlorpromazine : Mechanism of Chlorpromazine Binding to the Plant Plasma Membrane.氯丙嗪对UDP-葡萄糖:(1,3)-β-葡聚糖(胼胝质)合酶的抑制作用及紫外线诱导的化学修饰:氯丙嗪与植物质膜结合的机制
Plant Physiol. 1992 Dec;100(4):1927-33. doi: 10.1104/pp.100.4.1927.
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Lack of singlet oxygen formation by photoexcited promazine derivatives in aqueous and ethanolic solutions.光激发的丙嗪衍生物在水溶液和乙醇溶液中不产生单线态氧。
Radiat Environ Biophys. 1983;22(3):231-4. doi: 10.1007/BF01323713.
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Photoinduced free radicals from chlorpromazine and related phenothiazines: relationship to phenothiazine-induced photosensitization.
氯丙嗪及相关吩噻嗪类药物的光致自由基:与吩噻嗪类药物引起的光致敏作用的关系。
Environ Health Perspect. 1985 Dec;64:103-10. doi: 10.1289/ehp.8564103.