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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.
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K L Carpenter, and
M J Mitchinson, and
J N Skepper
July 1998,
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J N Skepper
March 2009,
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S J Hardwick, and
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M J Mitchinson, and
J N Skepper
January 1995,
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S J Hardwick, and
L Hegyi, and
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K L Carpenter, and
M J Mitchinson, and
J N Skepper
October 2000,
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S J Hardwick, and
L Hegyi, and
K Clare, and
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K L Carpenter, and
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December 2002,
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S J Hardwick, and
L Hegyi, and
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K L Carpenter, and
M J Mitchinson, and
J N Skepper
October 2016,
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S J Hardwick, and
L Hegyi, and
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K L Carpenter, and
M J Mitchinson, and
J N Skepper
March 1999,
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S J Hardwick, and
L Hegyi, and
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K L Carpenter, and
M J Mitchinson, and
J N Skepper
August 1997,
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S J Hardwick, and
L Hegyi, and
K Clare, and
N S Law, and
K L Carpenter, and
M J Mitchinson, and
J N Skepper
June 1999,
Kidney international,
S J Hardwick, and
L Hegyi, and
K Clare, and
N S Law, and
K L Carpenter, and
M J Mitchinson, and
J N Skepper
September 1996,
Zhongguo yao li xue bao = Acta pharmacologica Sinica,
