Accessibility navigation


Lysosomal oxidation of LDL alters lysosomal pH, induces senescence and increases secretion of pro-inflammatory cytokines in human macrophages

Ahmad, F. and Leake, D. S. (2019) Lysosomal oxidation of LDL alters lysosomal pH, induces senescence and increases secretion of pro-inflammatory cytokines in human macrophages. Journal of Lipid Research, 60. pp. 98-110. ISSN 1539-7262

[img]
Preview
Text - Accepted Version
· Please see our End User Agreement before downloading.

861kB

It is advisable to refer to the publisher's version if you intend to cite from this work. See Guidance on citing.

To link to this item DOI: 10.1194/jlr.M088245

Abstract/Summary

Objective We have shown that aggregated low density lipoproteins (LDL) is internalised by macrophages and oxidised in lysosomes by redox-active iron. We have now investigated if the lysosomal oxidation of LDL impairs lysosomal function and if a lysosomotropic antioxidant can prevent these alterations. Approach and Results LDL aggregated by sphingomyelinase (SMase-LDL) caused increased lysosomal lipid peroxidation in human monocyte-derived macrophages or THP-1 macrophage-like cells, as shown by a fluorescent probe, Foam-LPO. The pH of the lysosomes was increased considerably by lysosomal LDL oxidation as shown by Lysosensor Yellow/Blue and LysoTracker Red. SMase-LDL induced senescence-like properties in the cells as shown by β-galactosidase staining and levels of p53 and p21. Inflammation plays a key role in atherosclerosis. SMase-LDL treatment increased the LPS-induced secretion of TNF-α, IL-6 and MCP-1. The lysosomotropic antioxidant, cysteamine inhibited all of the above changes. Conclusions Targeting lysosomes with antioxidants, such as cysteamine, to prevent the intralysosomal oxidation of LDL might be a novel therapy for atherosclerosis.

Item Type:Article
Refereed:Yes
Divisions:Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Life Sciences > School of Biological Sciences > Biomedical Sciences
ID Code:80740
Publisher:American Society for Biochemistry and Molecular Biology

Downloads

Downloads per month over past year

University Staff: Request a correction | Centaur Editors: Update this record

Page navigation