Differential toxicities of air (mO-LDL) or copper-oxidized LDLs (Cu-LDL) toward endothelial cells.
In vivo low density protein (LDL) oxidation is a progressive phenomenon leading to the presence of minimally and highly oxidized LDLs in the subendothelial arterial space. Oxidized LDLs have been reported to be cytotoxic against endothelial cells. The goal of this study was to determine which of the minimally and highly oxidized LDLs were the most cytotoxic against bovine aortic endothelial cells (BAEC). Both the morphological aspect of the cells themselves, and LDH or MTT tests revealed that mO- or Cu-LDLs had similar cytotoxicity with up to 8 hours of oxidation, showing no relation with the level of LDL oxidation; for longer oxidation times, Cu-LDL cytotoxicity decreased. This phenomenon is linked to their different oxidation kinetics. Moreover, in the initial hours following BAEC incubation with mO- or Cu-LDLs, total cell glutathione dropped, whereas after 16 hours of incubation, highly oxidized Cu-LDL increased the glutathione level in the cell. The biphasic evolution of glutathione concentration corresponds to an autoprotective mechanism of cells against oxidized LDL cytotoxicity. This study suggests that the specific chemical characteristics of the different types of oxidized LDLs should always be precisely described in future assays devoted to studying the biological effects of what are known under the generic term as "oxidized LDLs". This precaution should prevent any confusion in interpreting different studies.
Furman
C
C
Département d'Athérosclérose and INSERM U 325, Pasteur Institute, Lille, France.
Martin-Nizard
F
F
Fruchart
J C
JC
Duriez
P
P
Teissier
E
E
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005453:Fluorescence; D005978:Glutathione / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism / Q000633:toxicity*; D008244:Lysophosphatidylcholines / Q000378:metabolism; D010084:Oxidation-Reduction; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D013997:Time Factors
D008077:Lipoproteins, LDL; D008244:Lysophosphatidylcholines; D017392:Thiobarbituric Acid Reactive Substances; C099252:oxidized low density lipoprotein; D000255:Adenosine Triphosphate; D002784:Cholesterol; D006861:Hydrogen Peroxide; D007770:L-Lactate Dehydrogenase; D005978:Glutathione