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High Uric Acid Activates the ROS-AMPK Pathway, Impairs CD68 Expression and Inhibits OxLDL-Induced Foam-Cell Formation in a Human Monocytic Cell Line, THP-1.

Authors :
Luo C
Lian X
Hong L
Zou J
Li Z
Zhu Y
Huang T
Zhang Y
Hu Y
Yuan H
Wen T
Zhuang W
Cai B
Zhang X
Hisatome I
Yamamoto T
Huang J
Cheng J
Source :
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology [Cell Physiol Biochem] 2016; Vol. 40 (3-4), pp. 538-548. Date of Electronic Publication: 2016 Nov 25.
Publication Year :
2016

Abstract

Background/aims: Hyperuricemia is part of the metabolic-syndrome cluster of abdominal obesity, impaired glucose tolerance, insulin resistance, dyslipidemia, and hypertension. Monocytes/macrophages are critical in the development of metabolic syndrome, including gout, obesity and atherosclerosis. However, how high uric acid (HUA) exposure affects monocyte/macrophage function remains unclear. In this study, we investigated the molecular mechanism of HUA exposure in monocytes/macrophages and its impact on oxidized low-density lipoprotein (oxLDL)-induced foam-cell formation in a human monocytic cell line, THP-1.<br />Methods: We primed THP-1 cells with phorbol-12-myristate-13-acetate (PMA) for differentiation, then exposed cells to HUA and detected the production of reactive oxygen species (ROS) and analyzed the level of phospho-AMPKα. THP-1 cells were pre-incubated with Compound C, an AMPK inhibitor, or N-acetyl-L-cysteine (NAC), a ROS scavenger, or HUA before PMA, to assess CD68 expression and phospho-AMPKα level. PMA-primed THP-1 cells were pre-treated with oxLDL before Compound C and HUA treatment. Western blot analysis was used to examine the levels of phospho-AMPKα, CD68, ABCG1, ABCA1, cyclooxygenase-2 (COX-2) and NF-κB (p65). Flow cytometry was used to assess ROS production and CD68 expression in live cells. Oil-red O staining was used to observe oxLDL uptake in cells.<br />Results: HUA treatment increased ROS production in PMA-primed THP-1 cells; NAC blocked HUA-induced oxidative stress. HUA treatment time-dependently increased phospho-AMPKα level in PMA-primed THP-1 cells. The HUA-induced oxidative stress increased phospho-AMPKα levels, which was blocked by NAC. HUA treatment impaired CD68 expression during cell differentiation by activating the AMPK pathway, which was reversed by Compound C treatment. Finally, HUA treatment inhibited oxLDL uptake in the formation of foam cells in THP-1 cells, which was blocked by Compound C treatment. HUA treatment significantly increased the expression of ABCG1 and reversed the oxLDL-reduced ABCG1 expression but did not affect the expression of ABCA1, NF-κB (p65) or COX-2.<br />Conclusions: HUA exposure activated the ROS-AMPK pathway, impaired CD68 expression, and inhibited oxLDL-induced foam-cell formation in a human monocytic cell line, THP-1.<br /> (© 2016 The Author(s) Published by S. Karger AG, Basel.)

Details

Language :
English
ISSN :
1421-9778
Volume :
40
Issue :
3-4
Database :
MEDLINE
Journal :
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
Publication Type :
Academic Journal
Accession number :
27889764
Full Text :
https://doi.org/10.1159/000452567