Exp Mol Med.  1999 Dec;31(4):165-173.

Oxidation-dependent effects of oxidized LDL: proliferation or cell death

• Han CY
• Kim Pak YM

Abstract

Oxidized low-density lipoprotein (oxLDL) induces a wide range of cellular responses to produce atherosclerotic lesion, but key factors determining the response are not understood. In this study, purified LDL was oxidized with copper sulfate, and its physical properties and the related biological responses were investigated. The average hydrodynamic diameter of the lightly oxidized LDL was approximately 25 nm and its Rf value relative to nLDL on agarose gel was between 1.0 and 1.25. The diameter of the extensively oxidized LDL was over 30 nm, the Rf value was over 2.0. A 24 h-exposure of resting RAW264.7 macrophage cells to 100 microg/ml of the lightly oxidized LDL induced proliferation and macrophage activation whereas the extensively oxidized LDL induced cell death at the same concentration. In contrast, 200 microg/ml of oxLDL caused cell death regardless of oxidation degree. Short incubation (4-6 h) of the highly oxidized LDL (100 microg/ml) also resulted in cell proliferation. OxLDL-induced cell death showed mixed characteristics of apoptosis and/or necrosis depending on the strength and duration of the insult. These results suggest that cellular responses induced by oxLDL be dependent on the oxidation degree, the duration of exposure, and the concentration of oxLDL. Copyright 2000 Academic Press.

Keyword

oxidized LDL; proliferation; cell death; macrophage

MeSH Terms

Animal
Apolipoproteins B/metabolism
Apoptosis/physiology
Apoptosis/drug effects
Cell Death/physiology*
Cell Division/physiology
Copper Sulfate/metabolism
Dose-Response Relationship, Drug
Human
Lipid Peroxidation
Lipids/metabolism
Lipoproteins, LDL/pharmacology
Lipoproteins, LDL/metabolism*
Macrophages/pathology
Macrophages/drug effects
Macrophages/cytology*
Mice
Necrosis
Oxidation-Reduction
Thiobarbituric Acid Reactive Substances/metabolism