albumin - publications

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1. Int J Biochem Cell Biol. 2012 Apr 3. [Epub ahead of print]

ER stress is associated with reduced ABCA-1 protein levels in macrophages treated
with advanced glycated albumin - Reversal by a chemical chaperone.

Castilho G, Okuda LS, Pinto RS, Nakandakare ER, Laurindo FR, Santos CX,
Passarelli M.

Lipids Laboratory (LIM 10), Heart Institute, Faculty of Medical Sciences,
University of São Paulo Medical School, São Paulo, SP, Brazil.

ATP-binding cassette transporter A1 mediates the export of excess cholesterol
from macrophages, contributing to the prevention of atherosclerosis. Advanced
glycated albumin (AGE-alb) is prevalent in diabetes mellitus and is associated
with the development atherosclerosis. Independent of changes in ABCA-1 mRNA
levels, AGE-alb induces oxidative stress and reduces ABCA-1 protein levels, which
leads to macrophage lipid accumulation. These metabolic conditions are known to
elicit endoplasmic reticulum (ER) stress. We sought to determine if AGE-albumin
induces ER stress and unfolded protein response (UPR) in macrophages and how
disturbances to the ER could affect ABCA-1 content and cholesterol efflux in
macrophages. AGE-alb induced a time-dependent increase in ER stress markers and
UPR markers. ABCA-1 content and cellular cholesterol efflux were reduced by 33%
and 47%, respectively, in macrophages treated with AGE-alb, and both were
restored by treatment with 4-phenyl butyric acid (a chemical chaperone that
alleviates ER stress), but not MG132 (a proteasome inhibitor). Tunicamycin, a
classical ER stress inductor, also impaired ABCA-1 expression and cholesterol
efflux (showing a decrease of 61% and 82%, respectively), confirming the
deleterious effect of ER stress in macrophage cholesterol accumulation.
Glycoxidation induces macrophage ER stress, which relates to the reduction in
ABCA-1 and in reverse cholesterol transport, endorsing the adverse effect of
macrophage ER stress in atherosclerosis. Thus, chemical chaperones that alleviate
ER stress may represent a useful tool for the prevention and treatment of
atherosclerosis in diabetes.

Copyright © 2012. Published by Elsevier Ltd.

PMID: 22497927 [PubMed - as supplied by publisher]