Treatment of cartilage proteoglycan aggregate with hydrogen
peroxide. Relationship between observed degradation products
and those that occur naturally during aging.
Author: Roberts CR; Mort JS; Roughley PJ
Source: Biochem J 1987 Oct 15; 247(2):349-57
The effects of treatment of purified neonatal human articular-
cartilage proteoglycan aggregate with H2O2 were studied. (1)
Exposure of proteoglycan aggregate to H2O2 resulted in
depolymerization of the aggregate and modification of the core
protein of both the proteoglycan subunits and the link proteins.
(2) Treatment of the proteoglycan aggregate with H2O2 rendered
the proteoglycan subunits unable to interact with hyaluronic
acid, with minimal change in their hydrodynamic size. (3)
Specific cleavages of the neonatal link proteins occurred.
The order in which the major products were generated and
their electrophoretic mobilities resembled the pattern
observed during human aging. (4) The proteolytic changes
in the link proteins were inhibited in the presence of
transition-metal-ion chelators, thiourea or tetramethylurea,
suggesting that generation of hydroxyl radicals from H2O2
by trace transition-metal ions via a site-specific Fenton
reaction may be responsible for the selective cleavages
observed. (5) Cleavage of the link proteins in proteoglycan
aggregates by H2O2 was shown to have a limited effect on
the susceptibility of these proteins to cleavage by trypsin.
(6) The relationship between these changes and those observed
in cartilage during human aging suggests that some of the
age-related changes in the structure of human cartilage
proteoglycan aggregate may be the result of radical-mediated