Different cytotoxic injuries induced by lysophosphatidylcholine and 7-ketocholesterol in mouse endothelial cells.
Lysophosphatidylcholine (LPC) and 7-ketocholesterol (7-KC) are two key components of oxidized low-density lipoprotein (oxLDL) and have been shown to injure endothelial cells derived from various species. This report examines LPC- and 7-KC-induced cell death in mouse aorta endothelial cells (MAECs). The presence and the mechanism of cell death were assessed with morphological criteria, Hoechst 33342 and propidium iodide fluorescence staining, and caspase-3 activity. The authors observed that 7-KC induced cell shrinkage, nuclear condensation, and caspase-3 activity. In contrast, LPC induced membrane rupture, nuclear expansion, and cell lysis. In addition, 7-KC induced a transient increase, whereas LPC induced a sustained increase in intracellular Ca2+ levels and production of reactive oxygen species (ROS). Antioxidants and calcium antagonists attenuated both 7-KC- and LPC-induced cell death. These findings suggest that 7-KC and LPC injure MAECs through differential mechanisms; LPC induces necrosis, 7-KC induces apoptosis, and the increase in intracellular Ca2+ levels and production of ROS are common mechanisms for these cytotoxic injuries.
Zhou
LiChun
L
Division of Cardiovascular Biology, Meharry Medical College, Nashville, Tennessee 37208, USA.
Shi
MingJian
M
Guo
ZhongMao
Z
Brisbon
Wendy
W
Hoover
Richard
R
Yang
Hong
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007653:Ketocholesterols / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D008858:Microscopy, Phase-Contrast; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism
D007653:Ketocholesterols; D008244:Lysophosphatidylcholines; D017382:Reactive Oxygen Species; D000255:Adenosine Triphosphate; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; C003001:7-ketocholesterol; D002118:Calcium