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Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D

1
Department of Cardiology, The People’s Hospital of Liaoning Province, Shenyang 110001, China
2
Department of Cardiology, The People’s Hospital of China Medical University, Shenyang 110001, China
3
Department of Cardiology, The First Hospital of China Medical University, Shenyang 110001, China
*
Author to whom correspondence should be addressed.
Academic Editor: Irmgard Tegeder
Int. J. Mol. Sci. 2017, 18(2), 436; https://doi.org/10.3390/ijms18020436
Received: 28 October 2016 / Revised: 12 January 2017 / Accepted: 13 February 2017 / Published: 17 February 2017
(This article belongs to the Section Biochemistry)
We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity. View Full-Text
Keywords: advanced glycation end products (AGEs); human umbilical vein endothelial cells (HUVECs); proliferation; migration; cathepsin D (CTSD); autophagy advanced glycation end products (AGEs); human umbilical vein endothelial cells (HUVECs); proliferation; migration; cathepsin D (CTSD); autophagy
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Li, Y.; Chang, Y.; Ye, N.; Dai, D.; Chen, Y.; Zhang, N.; Sun, G.; Sun, Y. Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D. Int. J. Mol. Sci. 2017, 18, 436.

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