RETINAL AGE PIGMENTS GENERATED BY SELF-ASSEMBLING LYSOSOMOTROPIC DETERGENTS
RETINAL AGE PIGMENTS GENERATED BY SELF-ASSEMBLING LYSOSOMOTROPIC DETERGENTS
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DOI：
10.1038/361724a0
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发表时间：
1993-02-25
期刊：
影响因子：
64.8
通讯作者：
LASKY, MR
中科院分区：
文献类型：
--
作者：
ELDRED, GE;LASKY, MR
真核有丝分裂后细胞衰老的一个通用生物标志物是随时间推移出现的自发荧光溶酶体残留体，称为老年色素或脂褐素颗粒1。它们在细胞衰老过程中的作用一直存在争议，但没有解决方案2。荧光团的身份和形成机制均尚未明确确定。积累大量老年色素的有丝分裂后细胞类型是眼部视网膜色素上皮2。我们现在已经使用快原子轰击串联质谱法和碰撞活化分析鉴定了这些颜料的主要橙色发射荧光团4。它是一种两性季胺，是视黄醛和乙醇胺的希夫碱反应产物。这种化合物应该表现出溶酶体去污剂行为，这将有助于解释该细胞中显示的许多与年龄相关的变化。这些结果表明席夫碱反应产物作为溶酶体胺在细胞年龄色素的形成中发挥着新的作用。
A UNIVERSAL biomarker of cellular ageing in eukaryotic post-mitotic cells is the appearance over time of autofluorescent lysosomal residual bodies called age pigments or lipofuscin granules1. Their role in the process of cellular ageing has been debated without resolution2. Neither the identity nor mechanism of formation of the fluorophores has been definitively determined. A post-mitotic cell type that accumulates large quantities of age pigments is the ocular retinal pigment epithelium2. We have now identified the major orange-emitting fluorophore of these pigments using fast-atom bombardment tandem mass spectrometry with collisional activation analysis4. It is an amphoteric quaternary amine that arises as a Schiff base reaction product of retinaldehyde and ethanolamine. This compound should display lysosomotropic detergent behaviour which would help explain many of the age-related changes shown in this cell. These results suggest a new role for Schiff base reaction products as lysosomotropic amines in the genesis of cellular age pigments.