Lysophosphatidylcholine induces apoptosis in human endothelial cells through a p38-mitogen-activated protein kinase-dependent mechanism.
Lysophosphatidylcholine (lysoPC) is a component of oxidized low density lipoprotein (LDL) and is involved in the pathogenesis of atherosclerosis and inflammation. Previous studies demonstrated that lysoPC can induce various protein kinases including tyrosine kinases, protein kinase C (PKC), and mitogen-activated protein kinases (MAPK) in vascular endothelial cells. However, the role of lysoPC-activated kinases remains undefined. In this study, we examined the effect of lysoPC on apoptosis and investigated the role of lysoPC-activated protein kinases in human umbilical vein endothelial cells (HUVEC). The presence of apoptosis was evaluated by morphological criteria, MTT assay, and electrophoresis of DNA fragments showing the characteristic apoptotic ladder, TUNEL analysis, and quantified as the proportion of hypodiploid cells by flow cytometry. The lysoPC induced apoptosis in a time- and dose-dependent manner. It stimulated the phosphorylation of extracellular signal-regulated kinase1/2 (ERK1/2) and p38-MAPK in HUVEC. The use of specific pharmacologic inhibitors indicated that the p38-MAPK-signaling pathway (SB203580) is required for lysoPC-induced apoptotic signals. Furthermore, lysoPC-induced apoptosis was inhibited by DEVD-FMK (a caspas-3/CPP32 inhibitor), suggesting involvement of an important segment in the apoptosis. These results demonstrate that lysoPC induces apoptosis in human endothelial cells through a p38-MAPK-dependent pathway.
Takahashi
Masafumi
M
Department of Cardiology, Jichi Medical School, Minamikawachi-machi, Tochigi 329-0498, Japan. masafumi@jichi.ac.jp
Okazaki
Hitoaki
H
Ogata
Yukiyo
Y
Takeuchi
Koichi
K
Ikeda
Uichi
U
Shimada
Kazuyuki
K
D000704:Analysis of Variance; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001161:Arteriosclerosis / Q000503:physiopathology; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008854:Microscopy, Electron; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism* / Q000502:physiology; D011336:Probability; D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000187:drug effects*; D014471:Umbilical Veins / Q000166:cytology; D048051:p38 Mitogen-Activated Protein Kinases
D008244:Lysophosphatidylcholines; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases