Retinal age pigments generated by self-assembling lysosomotropic detergents

Nature. 1993 Feb 25;361(6414):724-6. doi: 10.1038/361724a0.

Abstract

A universal biomarker of cellular ageing in eukaryotic postmitotic cells is the appearance over time of autofluorescent lysosomal residual bodies called age pigments or lipofuscin granules. Their role in the process of cellular ageing has been debated without resolution. Neither the identity nor mechanism of formation of the fluorophores has been definitively determined. A postmitotic cell type that accumulates large quantities of age pigments is the ocular retinal pigment epithelium. We have now identified the major orange-emitting fluorophore of these pigments using fast-atom bombardment tandem mass spectrometry with collisional activation analysis. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cellular Senescence / physiology*
  • Chromatography, Thin Layer
  • Detergents / pharmacology*
  • Humans
  • Lysosomes / drug effects
  • Lysosomes / physiology*
  • Magnetic Resonance Spectroscopy
  • Pigment Epithelium of Eye / chemistry
  • Pigment Epithelium of Eye / drug effects
  • Pigment Epithelium of Eye / physiology*
  • Retinal Pigments / isolation & purification
  • Retinal Pigments / metabolism*
  • Retinaldehyde / isolation & purification
  • Retinaldehyde / metabolism
  • Schiff Bases
  • Spectrometry, Mass, Fast Atom Bombardment
  • Spectrophotometry

Substances

  • Detergents
  • Retinal Pigments
  • Schiff Bases
  • Retinaldehyde