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Experimental Diabetes Research
Volume 2012 (2012), Article ID 356487, 10 pages
http://dx.doi.org/10.1155/2012/356487
Research Article

Amelioration of Glucolipotoxicity-Induced Endoplasmic Reticulum Stress by a “Chemical Chaperone” in Human THP-1 Monocytes

1Department of Cell and Molecular Biology, Madras Diabetes Research Foundation and Dr. Mohans’ Diabetes Specialities Centre, Chennai 600086, India
2Centre for Biotechnology, Anna University, Chennai 600025, India

Received 17 December 2011; Accepted 13 February 2012

Academic Editor: Rangasamy Sampathkumar

Copyright © 2012 Raji Lenin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Chronic ER stress is emerging as a trigger that imbalances a number of systemic and arterial-wall factors and promote atherosclerosis. Macrophage apoptosis within advanced atherosclerotic lesions is also known to increase the risk of atherothrombotic disease. We hypothesize that glucolipotoxicity might mediate monocyte activation and apoptosis through ER stress. Therefore, the aims of this study are (a) to investigate whether glucolipotoxicity could impose ER stress and apoptosis in THP-1 human monocytes and (b) to investigate whether 4-Phenyl butyric acid (PBA), a chemical chaperone could resist the glucolipotoxicity-induced ER stress and apoptosis. Cells subjected to either glucolipotoxicity or tunicamycin exhibited increased ROS generation, gene and protein (PERK, GRP-78, IRE1α, and CHOP) expression of ER stress markers. In addition, these cells showed increased TRPC-6 channel expression and apoptosis as revealed by DNA damage and increased caspase-3 activity. While glucolipotoxicity/tunicamycin increased oxidative stress, ER stress, mRNA expression of TRPC-6, and programmed the THP-1 monocytes towards apoptosis, all these molecular perturbations were resisted by PBA. Since ER stress is one of the underlying causes of monocyte dysfunction in diabetes and atherosclerosis, our study emphasize that chemical chaperones such as PBA could alleviate ER stress and have potential to become novel therapeutics.