Lipofuscin-like substances accumulate rapidly in brain, retina and internal organs with cysteine protease inhibition

Advances in Experimental Medicine and Biology
G O IvyK Kitani

Abstract

The protease inhibitor, leupeptin, has been previously shown to cause an accumulation of lysosomally associated intracytoplasmic dense bodies resembling lipofuscin when administered intraventricularly to the brains of young rats (Ivy et al., Science, 226:985, 1984). These findings support the idea that lipofuscin formation during normal aging involves perturbed proteolytic degradation. In the current study, we delineate more precisely the proteolytic mechanisms in question and examine the effects of protease inhibition on other tissues and species. Four sets of experiments were done. In the first, rats were administered leupeptin (L; an inhibitor of cysteine and some serine proteases), E-64C (a cysteine protease inhibitor), chloroquine (C; a lysosomal enzyme inhibitor), aprotinin (A; a serine protease inhibitor) or physiological saline (S) into the lateral ventricle of the brain at a constant rate for two weeks using an osmotic mini-pump. In the second set, beagle dogs were administered L or S intraventricularly in a similar fashion. In the third set, young rats received intraocular injections of L, E64C, C, A or S from 1 to 9 days at 24 hr intervals. In the fourth set, young rats and mice were administered L, E-64C or S intrap...Continue Reading

Citations

Jul 1, 1994·The Anatomical Record·T Barka, H van der Noen
Jun 1, 2012·Toxicologic Pathology·Kendall S FrazierAxel Bube
Oct 2, 2003·Physiological Genomics·Hisashi IdaLeonard M Hjelmeland
Nov 9, 2014·Brain Structure & Function·Emmanuel P GilissenJean-Pierre Brion
Oct 15, 2013·The Anatomical Record : Advances in Integrative Anatomy and Evolutionary Biology·Emmanuel P Gilissen, Ludmilla Staneva-Dobrovski
Feb 7, 2004·Archives of Gerontology and Geriatrics·Martin L Katz, W Gerald Robison
Jun 5, 2002·Mechanisms of Ageing and Development·Martin L Katz

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