S. Miyata et al., ACCUMULATION OF PYRRALINE-MODIFIED ALBUMIN IN PHAGOCYTES DUE TO REDUCED DEGRADATION BY LYSOSOMAL-ENZYMES, The Journal of biological chemistry, 272(7), 1997, pp. 4037-4042
Previous studies suggested that the interaction between proteins modif
ied by advanced glycation end products (AGEs) and cells, such as macro
phages, may be involved in diabetic angiopathy. Pyrraline is one of th
e AGEs and known to be elevated in plasma of diabetic rats and humans,
and is present in vascular lesions of diabetic and elderly subjects.
We examined whether modification of albumin by pyrraline influences it
s degradation by macrophage-like cell line, P388D(1) cells. Degradatio
n of pyrraline-modified albumin by these cells was diminished, causing
accumulation of the albumin in these cells. The susceptibility of pyr
raline-modified albumin to lysosomal proteolytic enzymes was reduced b
y approximately 40% in vitro, while lysosomal activity in the cells pe
r se was not affected. This phenomenon was also observed when human mo
nocytes were used instead of P388D(1) cells. Our results suggest that
accumulation of pyrraline-modified albumin in P388D, cells is due to t
he reduced susceptibility of the protein to lysosomal enzymatic degrad
ation. Such alterations in the interaction between AGEs-modified prote
in and phagocytes may contribute to angiopathy in elderly subjects and
patients with diabetes.