Apoptosis in Human Monocyte‐macrophages Exposed to Oxidized Low Density Lipoprotein

Abstract

This study has demonstrated the toxicity to human monocyte-macrophages of low-density lipoprotein (LDL) which had been artificially oxidized using copper sulphate. The assays of cell damage used were tritiated adenine release, neutral red staining, lactate dehydrogenase leakage, and MTT dye reduction. Toxicity was concentration- and time-dependent. Exposure to native LDL under the same conditions did not result in toxicity. Transmission electron microscopy of cells exposed to oxidized LDL showed characteristic changes of apoptosis, including chromatin condensation and a decrease in cell volume. There was extensive loss of cell surface protrusions and evidence of the phagocytosis of apoptotic cells by neighbouring monocyte-macrophages. Apoptotic features preceded the increased membrane permeability revealed by the release of radioactivity from cells preloaded with tritiated adenine and by lactate dehydrogenase leakage. DNA fragmentation was indicated by nick end-labelling using the terminal transferase enzyme (TUNEL). The number of TUNEL-positive cells was markedly greater in cells exposed to oxidized LDL, compared with those incubated as no-additions controls. Inhibition of de novo protein synthesis with cycloheximide and of Ca2+/Mg(2+)-activated endonuclease activity with aurintricarboxylic acid or zinc ion did not inhibit the toxicity produced by oxidized LDL.

Mitochondrial Cholesterol Transporter, StAR, Inhibits Human THP‐1 Monocyte‐Derived Macrophage Apoptosis

“…Increasing numbers of reports indicate that Ox-LDL is cytotoxic to macrophages and contributes to macrophage apoptosis [31][32][33], which may relate to downregulating expression of the anti-apoptotic genes Bcl-2 and up-regulating the pro-apoptotic genes Bax and Caspases [34][35][36][37]. However, in the present study, the apoptotic index, including morphology, DNA ladder, and the quantity of apoptotic and necrotic cells, in groups treated with or without Ox-LDL were not obviously different.…”

Toxicity and imaging of multi-walled carbon nanotubes in human macrophage cells

“…One thousand cells were indexed for each exposure (control, 5 and 20 mg/mL), and the entire experimental process repeated four times for statistical analysis. Cells were determined as either apoptotic (shrunken, vacuoles in a condensed cytoplasm, heavily capped chromatin), necrotic (electron-lucent with cytoplasmic and nuclear contents appearing leached out) or healthy by comparing cell morphology to reference images from previous studies [31].…”

LOX-1/LOXIN: The Yin/Yang of Atheroscleorosis

“…Thus, oxLDL levels show a significant positive correlation with the severity of acute coronary syndromes such as myocardial infarction (MI) and unstable angina, and the more severe lesions contain a significantly higher percentage of oxLDLpositive macrophages [8]. According to this scenario, it has been shown that oxLDL is cytotoxic to cultured cells and induces apoptosis and necrosis of vascular endothelial cells, smooth muscle cells (SMCs), and macrophages [9][10][11][12]. These processes have been proposed to lead to plaque vulnerability and potential rupture, which is ultimately responsible for acute atherothrombotic vascular occlusion and tissue infarction.…”