Disulfide bond formation in the eye lens.
Disulfide bond formation in the eye lens.
复制标题
DOI：
10.1073/pnas.82.23.7965
复制
发表时间：
1985-12
影响因子：
11.1
通讯作者：
N. Yu;D. DeNagel;P. Pruett;J. Kuck
中科院分区：
文献类型：
--
作者：
N. Yu;D. DeNagel;P. Pruett;J. Kuck
本研究利用激光拉曼光谱作为无创性微探针，在完整的活体透镜中研究了老化和白内障形成过程中透镜中-SH基团的分布和处置。在该过程中，-SH和-S-S-给出独特的离散拉曼信号（在2580和508 cm-1处），其可用于计算透镜的非常小体积中的相对浓度。我们目前的证据表明，一个意想不到的和显着的差异，这些群体之间的小鼠透镜和豚鼠和man. The小鼠透镜核表现出急剧下降的-SH浓度老化1至6个月，伴随着，有上升-S-S-的幅度相当，表明直接转换。然而，豚鼠的透镜在核S-S-的年龄依赖性变化方面是完全不同的：在6个月至5岁之间没有变化。在人类透镜中-S-S-的行为与豚鼠透镜中完全相同：水平较低，在9至65岁之间不随年龄变化。关于核-SH，后两种晶状体显示出随着年龄的增长而降低，但不像在老化小鼠透镜核中发现的接近于零。这些涉及晶状体-SH和-S-S-的差异似乎与小鼠透镜中的硬核和豚鼠和人类晶状体中的软核相关。老年但透明的小鼠透镜中相对高水平的-S-S-不支持蛋白质聚集涉及分子间-S-S-键的形成必然是核性白内障的重要原因的观点。豚鼠透镜核中-SH的小但显著的年龄相关性抑制，而没有任何-S-S-的积累，这可以解释为谷胱甘肽（GSH）氧化和随后由透镜挤出谷胱甘肽二硫化物（GSSG）的结果。我们提出谷胱甘肽的氧化是通过与蛋白质二硫键基团反应产生蛋白质巯基（PSH）和谷胱甘肽和蛋白质的混合二硫化物进行的;混合二硫化物能够被谷胱甘肽还原酶和NADPH还原，产生原始PSH和GSSG，其从透镜中挤出。这一机制在豚鼠和人晶状体中是否比在小鼠透镜中更活跃仍有待确定。
The disposition and disposal of the -SH groups of the lens during aging and cataractogenesis have been investigated by laser Raman spectroscopy as a noninvasive microprobe in the intact living lens. In this procedure -SH and -S-S- give unique discrete Raman signals (at 2580 and 508 cm-1) that may be used to calculate relative concentrations in a very small volume of the lens. We present evidence showing an unexpected and remarkable difference with respect to these groups between the mouse lens and the lenses of guinea pig and man. The mouse lens nucleus exhibits a precipitous fall in the -SH concentration on aging from 1 to 6 months; concomitantly, there is a rise in -S-S- of comparable magnitude, indicating a direct conversion. The guinea pig lens, however, is quite different with respect to the age-dependent change in nuclear -S-S-: there is none between 6 months and 5 years. In the human lens -S-S- behaves exactly as in the guinea pig lens: the level is low and does not change with age between 9 and 65 years. With respect to nuclear -SH, these two latter species of lenses show some decrease with age but nothing like the approach to zero found in the aging mouse lens nucleus. These differences involving lenticular -SH and -S-S- appear to be correlated with the hard nucleus in the mouse lens and the softer nuclei of lenses in guinea pigs and humans. The relatively high level of -S-S- in the old but clear mouse lens does not support the idea that protein aggregation involving formation of intermolecular -S-S- bonds is necessarily an important cause of nuclear cataract. The small but significant age-related depression of -SH in guinea pig lens nuclei without any accumulation of -S-S- may be explained as a result of glutathione (GSH) oxidation and subsequent extrusion of glutathione disulfide (GSSG) by the lens. We propose that the oxidation of glutathione proceeds by reaction with protein disulfide groups to yield protein sulfhydryl (PSH) and a mixed disulfide of glutathione and protein; the mixed disulfide is capable of being reduced by glutathione reductase and NADPH, yielding the original PSH and GSSG, which is extruded from the lens. It remains to be determined if this mechanism is more active in guinea pig and human lenses than in the mouse lens.