Glycosaminoglycans from aged human hippocampus have altered capacities to regulate trophic factors activities but not Aβ42 peptide toxicity.
Glycosaminoglycans (GAGs) are major extracellular matrix components known to tightly regulate cell behavior by interacting with tissue effectors as trophic factors and other heparin binding proteins. Alterations of GAGs structures might thus modify the nature and extent of these interactions and alter tissue integrity. Here, we studied levels and composition of GAGs isolated from adult and aged human hippocampus and investigated if their changes can influence the function of important trophic factors and the Aβ42 peptide toxicity. Biochemical analyses showed that heparan sulfates are increased in the aged hippocampus. Moreover, GAGs from aged hippocampus showed altered capacities to regulate trophic factor activities without changing their capacities to protect cells from Aβ42 toxicity, compared to adult hippocampus GAGs. Structural alterations in GAGs from elderly were suggested by differential transcripts levels of key biosynthetic enzymes. C5-epimerase and 2-OST expressions were decreased while NDST-2 and 3-OST-4 were increased; in contrast, heparanase expression was unchanged. Results suggest that alteration of GAGs in hippocampus of aged subjects could participate to tissue impairment during aging.
Laboratoire CRRET, CNRS EAC 7149, Faculté des Sciences et Technologie, Université Paris-Est, Créteil, France.
Minh Bao
MB
Huynh
Joao
J
Villares
Julia Elisa Sepúlveda
JE
Díaz
Stephy
S
Christiaans
Gilles
G
Carpentier
Mohand Ouidir
MO
Ouidja
Ludmilla
L
Sissoeff
Rita
R
Raisman-Vozari
Dulce
D
Papy-Garcia
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000473:pathology* / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000502:physiology* / Q000633:toxicity*; D005260:Female; D006025:Glycosaminoglycans / Q000502:physiology*; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000502:physiology* / Q000633:toxicity*; D055815:Young Adult
D016229:Amyloid beta-Peptides; D006025:Glycosaminoglycans; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)