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Oxidative Medicine and Cellular Longevity
Volume 2017 (2017), Article ID 8419035, 10 pages
Research Article

Phagocytosis of Advanced Glycation End Products (AGEs) in Macrophages Induces Cell Apoptosis

1Department of Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan
2Department of Pharmacology, School of Pharmacy, Shujitsu University, Okayama 703-8516, Japan
3Department of Pharmacology, Faculty of Medicine, Kinki University, Osakasayama 589-8511, Japan

Correspondence should be addressed to Masahiro Nishibori

Received 4 August 2017; Revised 15 November 2017; Accepted 22 November 2017; Published 20 December 2017

Academic Editor: Mark Crabtree

Copyright © 2017 Yuan Gao 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.


Advanced glycation end products (AGEs) are the products of a series of nonenzymatic modifications of proteins by reducing sugars. AGEs play a pivotal role in development of diabetic complications and atherosclerosis. Accumulation of AGEs in a vessel wall may contribute to the development of vascular lesions. Although AGEs have a diverse range of bioactivities, the clearance process of AGEs from the extracellular space, including the incorporation of AGEs into specific cells, subcellular localization, and the fate of AGEs, remains unclear. In the present study, we examined the kinetics of the uptake of AGEs by mouse macrophage J774.1 cells in vitro and characterized the process. We demonstrated that AGEs bound to the surface of the cells and were also incorporated into the cytoplasm. The temperature- and time-dependent uptake of AGEs was saturable with AGE concentration and was inhibited by cytochalasin D but not chlorpromazine. We also observed the granule-like appearance of AGE immunoreactivity in subcellular localizations in macrophages. Higher concentrations of AGEs induced intracellular ROS and 4-HNE, which were associated with activation of the NF-κB pathway and caspase-3. These results suggest that incorporation of AGEs occurred actively by endocytosis in macrophages, leading to apoptosis of these cells through NF-κB activation.