Journal ArticleDOI
Inhibitors of lysosomal enzymes: accumulation of lipofuscin-like dense bodies in the brain
TLDR
Injections of leupeptin or chloroquine into the brains of young rats induced the formation of lysosome-associated granular aggregates which closely resembled the ceroid-lipofuscin that accumulates in certain disease states and during aging.Abstract:
Injections of leupeptin (a thiol proteinase inhibitor) or chloroquine (a general lysosomal enzyme inhibitor) into the brains of young rats induced the formation of lysosome-associated granular aggregates (dense bodies) which closely resembled the ceroid-lipofuscin that accumulates in certain disease states and during aging The dense material increased in a dose- and time-dependent fashion and was differentially distributed across brain regions and cell types These observations provide clues to the origins of ceroid-lipofuscin and suggest means for studying the consequences of its accumulationread more
Citations
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Journal ArticleDOI
The Free Radical Theory of Aging Matures
Kenneth B. Beckman,Bruce N. Ames +1 more
TL;DR: The status of the free radical theory of aging is reviewed, by categorizing the literature in terms of the various types of experiments that have been performed, which include phenomenological measurements of age-associated oxidative stress, interspecies comparisons, dietary restriction, and the ongoing elucidation of the role of active oxygen in biology.
Journal ArticleDOI
Protein damage and degradation by oxygen radicals. I. general aspects.
TL;DR: The results indicate a general sensitivity of proteins to oxygen radicals and indicate that proteins which have been denatured by .OH can be recognized and degraded rapidly and selectively by intracellular proteolytic systems.
Journal ArticleDOI
Degradation of oxidized proteins in mammalian cells.
TL;DR: By minimizing protein aggregation and cross‐linking and by removing potentially toxic protein fragments, proteasome plays a key role in the overall antioxidant defenses that minimize the ravages of aging and disease.
Journal ArticleDOI
Degradation of oxidized proteins by the 20S proteasome.
TL;DR: New experiments indicate that conditional mutational inactivation of the E1 ubiquitin-activating enzyme does not affect the degradation of oxidized proteins, further strengthening the hypothesis that oxidatively modified proteins are degraded in an ATP-independent, and ubiquit in-dependent, manner by the 20S proteasome.
Journal ArticleDOI
Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis
David E. Sleat,Robert J. Donnelly,Henry Lackland,Henry Lackland,Chang Gong Liu,Istvan Sohar,Istvan Sohar,Raju K. Pullarkat,Peter Lobel,Peter Lobel +9 more
TL;DR: In this paper, the mannose 6-phosphate modification of newly synthesized lysosomal enzymes was used as an affinity marker, and a single protein was identified that is absent in LINCL.
References
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Journal ArticleDOI
Protein degradation in cultured cells. II. The uptake of chloroquine by rat fibroblasts and the inhibition of cellular protein degradation and cathepsin B1.
Maurice Wibo,Brian Poole +1 more
TL;DR: It is concluded that chloroquine impairs the breakdown of cellular proteins after these have entered the lysosome system, probably through inhibition of cathepsin B1.
Journal ArticleDOI
Studies in Tay-Sachs disease. II. Ultrastructure of the cerebrum.
Robert D. Terry,Martin H. Weiss +1 more
Journal ArticleDOI
Biological activities of leupeptins.
Takaaki Aoyagi,Setsuko Miyata,Masako Nanbo,Fukiko Kojima,Meiki Matsuzaki,Masaaki Ishizuka,Tomio Takeuchi,Hamao Umezawa +7 more
TL;DR: The effects of leupeptins on thrombokinase, thrombin, plasmin, trypsin, papain, kallikrein and α-chymotrypsin were compared with those of e-aminocaproic acid, trans-4-aminomethylcyclohexanecarboxylic acid, soybeantrypsin inhibitor and trasylol.
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