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Formation of a new class of aging pigments in human lens

人类晶状体中新型老化色素的形成

基本信息

批准号：
63480174
负责人：
MANABE Shigeo
金额：
$ 3.46万
依托单位：
University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1988
资助国家：
日本
起止时间：
1988 至 1989
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-63480174/
关键词：
aging pigment fluorogen human lens heterocyclic amine carcinogen amino acid pyrolysate レンズ白内障

项目摘要

Previous studies on cataractous and normal lenses have revealed the age-related accumulation of fluorogens in the human lens. Although some fluorescent compounds such as beta-carboline derivatives, anthranilic acid and 3,3'-bityrosine have been identified in human lens, most of fluorescent compounds in human lens have not been identified. In this investigation, we found four fluorescent compounds as new fluorogens in lens and investigated the age-related accumulation of these compounds. The presence of these compounds in lens have not been reported and these four compounds are structurally a family of heterocyclic amines. Later, these heterocyclic amines were found to be carcinogenic glutamic acid pyrolysis products products (Glu-P-1, Glu-P-2) and carcinogenic tryptophan pyrolysis products (Trp-P-1, Trp-P-2) which had been reported to be present as carcinogens in cooked foodstuffs. these carcinogenic heterocyclic amines are strong fluorescent compounds and their contents in denatured lens proteins are significantly higher than those in carcinogenic tryptophan pyrolysis products may be formed in lens under the certain conditions. These results suggest that the carcinogenic heterocyclic amines are present as aging pigments in human lens, but also might open new vistas about the determination of the relationship between aging and carcinogenesis.

之前对白内障和正常晶状体的研究已经揭示了人类晶状体中与年龄相关的荧光素积累。虽然已经在人类晶状体中发现了一些荧光化合物，如β-咔啉类化合物、邻氨基苯甲酸和3，3‘-二氢酪氨酸等，但人类晶状体中的大多数荧光化合物都没有被鉴定出来。在这项研究中，我们发现了四种荧光化合物作为新的荧光体在晶状体中，并研究了这些化合物随年龄的积累。这些化合物在晶体中的存在还没有报道，这四个化合物在结构上是一个杂环胺家族。后来，这些杂环胺被发现是致癌的谷氨酸热解产物(Glu-P-1，Glu-P-2)和致癌色氨酸热解产物(Trp-P-1，Trp-P-2)，这两种产物已被报道为熟食中的致癌物质。这些致癌杂环胺是强荧光化合物，其在变性晶状体蛋白中的含量显着高于致癌色氨酸的含量，在一定条件下晶状体中可能会生成色氨酸热解产物。这些结果表明，致癌杂环胺以老化色素的形式存在于人类晶状体中，也可能为确定衰老与致癌的关系开辟新的前景。