Monitoring the apoptotic process induced by oxidized low-density lipoprotein in Jurkat T-lymphoblast and U937 monocytic human cell lines.
Cell death is a major event in the pathophysiology of atherosclerosis. Oxidized low-density lipoprotein (Ox-LDL), which plays a key role in the atherogenesis, has a powerful cytotoxic effect and causes necrosis or apoptosis of different types of cells. In the present work we studied the mechanism of cell death in two model systems: T lymphocytes and monocytes cell line, exposed to Ox-LDL. Ox-LDL, but not native low-density lipoprotein (LDL), was found to be cytotoxic to both cell types in a dose and time dependent manner. Apoptotic cell death was analyzed by evaluating cell size, nucleus DNA content and plasma membrane asymmetry. Early cytoplasmic condensation resulting from cell shrinkage was measured by monitoring fluorescence polarization (FP) of fluorescein labeled cells. The radical scavenger superoxide dismutase (SOD), in a time- and dose-dependent manner, reduced the apoptotic effect of Ox-LDL. Hyperpolarization of fluorescein-labeled cells preceded the appearance of phosphatidylserine (PS) on the plasma membrane. This sensitive parameter for early apoptosis detected different cell death kinetics, as well as varying sensitivity to the inhibitory effect of SOD in monocytes and lymphocytes. Such data suggest that reactive oxygen species generation are involved in Ox-LDL-induced apoptosis and that monocytes are more susceptible to cell death triggered by oxidative stress.
Zurgil
Naomi
N
The Biophysical Interdisciplinary Jerome Schottenstein Center for the Research and Technology of the Cellome, Department of Physics, Bar Ilan University, Ramat Gan, Israel.
Solodeev
Inna
I
Gilburd
Boris
B
Shafran
Yana
Y
Afrimzon
Elena
E
Avtalion
Rami
R
Shoenfeld
Yehuda
Y
Deutsch
Mordechai
M
D017209:Apoptosis / Q000187:drug effects*; D048429:Cell Size / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D019169:Jurkat Cells; D008077:Lipoproteins, LDL / Q000008:administration & dosage*; D010084:Oxidation-Reduction; D020298:U937 Cells
D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein