Low density lipoprotein undergoes oxidation within lysosomes in cells

Wen, Y. and Leake, D. S. ORCID: https://orcid.org/0000-0002-1742-6134 (2007) Low density lipoprotein undergoes oxidation within lysosomes in cells. Circulation Research, 100. pp. 1337-1343. ISSN 0009-7330 doi: 10.1161/CIRCRESAHA.107.151704

Abstract/Summary

The oxidised low density lipoprotein (LDL) hypothesis of atherosclerosis proposes that LDL undergoes oxidation in the interstitial fluid of the arterial wall. We have shown that aggregated (vortexed) nonoxidised LDL was taken up by J774 mouse macrophages and human monocyte-derived macrophages and oxidised intracellularly, as assessed by the microscopic detection of ceroid, an advanced lipid oxidation product. Confocal microscopy showed that the ceroid was located in the lysosomes. To confirm these findings, J774 macrophages were incubated with acetylated LDL, which is internalised rapidly to lysosomes, and then incubated (chase incubation) in the absence of any LDL. The intracellular levels of oxysterols, measured by HPLC, increased during the chase incubation period, showing that LDL must have been oxidised inside the cells. Furthermore, we found that this oxidative modification was inhibited by lipid-soluble antioxidants, an iron chelator taken up by fluid-phase pinocytosis and the lysosomotropic drug chloroquine, which increases the pH of lysosomes. The results indicate that LDL oxidation can occur intracellularly, most probably within lysosomes.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/7725
Item Type	Article
Refereed	Yes
Divisions	Life Sciences > School of Biological Sciences > Biomedical Sciences Interdisciplinary centres and themes > Institute for Cardiovascular and Metabolic Research (ICMR)
Publisher	American Heart Association
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