Cathepsin D is one of the major enzymes involved in intracellular degradation of AGE-modified proteins.
Oxidized and cross-linked modified proteins are known to accumulate in ageing. Little is known about whether the accumulation of proteins modified by advanced glycation end products (AGEs) is due to an affected intracellular degradation. Therefore, this study was designed to determine whether the intracellular enzymes cathepsin B, cathepsin D and the 20S proteasome are able to degrade AGE-modified proteins in vitro. It shows that AGE-modified albumin is degraded by cathepsin D, while cathepsin B was less effective in the degradation of aldehyde-modified albumin and the 20S proteasome was completely unable to degrade them. Mouse primary embryonic fibroblasts isolated from a cathepsin D knockout animals were found to have an extensive intracellular AGE-accumulation, mainly in lysosomes, and a reduction of AGE-modified protein degradation compared to cells isolated from wild type animals. In summary, it can be assumed that cathepsin D plays a significant role in the removal of AGE-modified proteins.
Grimm
Stefanie
S
Institute of Biological Chemistry and Nutrition, University of Hohenheim, Stuttgart, Germany.
Ernst
Lisa
L
Grötzinger
Nicole
N
Höhn
Annika
A
Breusing
Nicolle
N
Reinheckel
Thomas
T
Grune
Tilman
T
D000418:Albumins / Q000737:chemistry / Q000378:metabolism; D000818:Animals; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D005347:Fibroblasts / Q000378:metabolism; D041981:Gastrointestinal Tract / Q000201:enzymology; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006037:Glyoxal / Q000737:chemistry / Q000378:metabolism; D042541:Intracellular Space / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010447:Peptide Hydrolases / Q000378:metabolism; D011499:Protein Processing, Post-Translational / Q000235:genetics; D011506:Proteins / Q000378:metabolism*
D000418:Albumins; D017127:Glycation End Products, Advanced; D011506:Proteins; D006037:Glyoxal; D010447:Peptide Hydrolases; D002402:Cathepsin D; C533923:Ctsd protein, mouse