AGGREGATION OF GAMMA-GLOBULIN BY CIS-DIAMINEDICHLOROPLATINUM(II) - ALTERATION OF FC REGION AND RESTORATION BY DIETHYLDITHIOCARBAMATE
AGGREGATION OF GAMMA-GLOBULIN BY CIS-DIAMINEDICHLOROPLATINUM(II) - ALTERATION OF FC REGION AND RESTORATION BY DIETHYLDITHIOCARBAMATE
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DOI：
10.1016/0378-5173(95)00067-s
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发表时间：
1995-10-03
影响因子：
5.8
通讯作者：
YOTSUYANAGI, T
中科院分区：
文献类型：
--
作者：
OHTA, N;CHEN, D;YOTSUYANAGI, T
含有 IgG 的人丙种球蛋白通常通过其 Fc 区显示出与蛋白 A 的结合能力。当纯化的人丙种球蛋白与顺式二氯二氨铂 (II) (顺式 DDP) 一起孵育时，观察到与蛋白 A 的结合减少。另一方面，人血浆中的丙种球蛋白在相似剂量下仅表现出蛋白 A 结合略有下降，这可能是由于血浆中的其他内部物质通过捕获顺式 DDP 所致。用顺式 DDP 预处理的丙种球蛋白的减少导致 H 和 HL 成分的量显着减少，而 L 链正常检测到。这些结果表明cis-DDP影响位于Fe区域的H-H链间的二硫(S-S)键。我们已经证明顺式-DDP引起γ-球蛋白聚合及其S-S键断裂(Chen等人，Int.J.Pharm.，106(1994)249-253)。二乙基二硫代氨基甲酸酯 (DDTC) 通过减少 S-S 键、聚合以及降低 γ-球蛋白与蛋白 A 的结合能力，部分恢复了顺式-DDP 对 γ-球蛋白的影响。由于已知 DDTC 很容易裂解 Pt-S 键，因此 Pt-S 键可能是恢复这种γ-球蛋白-顺-DDP 相互作用的原因。
Human gamma-globulin containing IgGs generally shows a binding ability to protein A through its Fc region. When purified human gamma-globulin was incubated with cis-diamminedichloroplatinum(II) (cis-DDP), reduced binding to protein A was observed. On the other hand, gamma-globulin in human plasma showed only a slight decrease in protein A binding at similar doses, due probably to other internal substances in plasma by trapping cis-DDP. Reduction of gamma-globulin pretreated with cis-DDP resulted in significantly decreased amounts of the H and HL components, whereas the L chain was normally detected. These results suggest that cis-DDP affects the disulfide(S-S) bond(s) in the inter H-H chains which locate in the Fe region. We have demonstrated that cis-DDP causes gamma-globulin polymerization and its S-S bond cleavage (Chen et al., Int. J. Pharm., 106 (1994) 249-253). Diethyldithiocarbamate (DDTC) partly restored these effects of cis-DDP on gamma-globulin in terms of the decreased S-S bonds, polymerization, and the reduced binding ability of gamma-globulin to protein A. Since DDTC is known to easily cleave the Pt-S bond, Pt-S bonds are likely to be responsible for the restoration of this gamma-globulin-cis-DDP interaction.