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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Castilho, Gabriela [1] ; Okuda, Ligia S. [1] ; Pinto, Raphael S. [1] ; Iborra, Rodgiro T. [1] ; Nakandakare, Edna R. [1] ; Santos, Celio X. [2] ; Laurindo, Francisco R. [2] ; Passarelli, Marisa [1]
Total Authors: 8
[1] Univ Sao Paulo, Fac Med Sci, Lipids Lab LIM 10, BR-01246000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med Sci, Vasc Biol Lab, Inst Heart, BR-01246000 Sao Paulo - Brazil
Total Affiliations: 2
Document type: Journal article
Source: INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY; v. 44, n. 7, p. 1078-1086, JUL 2012.
Web of Science Citations: 18

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 of atherosclerosis. Independently 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-alb 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 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. (C) 2012 Elsevier Ltd. All rights reserved. (AU)

FAPESP's process: 09/53869-9 - Influence of modified albumin from Diabetes mellitus in the differential expression of genes and lipid flux in macrophages: the role of reactive oxygen species, inflammatory markers and endoplasmic reticulum stress
Grantee:Marisa Passarelli
Support Opportunities: Regular Research Grants