Luteolin inhibits lysophosphatidylcholine-induced apoptosis in endothelial cells by a calcium/mitocondrion/caspases-dependent pathway.
Luteolin, a naturally occurring polyphenol flavonoid, has demonstrated some beneficial modulation toward the endothelium. This study aims to investigate the effects of luteolin on lysophosphatidylcholine (LPC)-induced apoptosis, a key event in the pathogenesis of atherosclerosis, in endothelial cells. Luteolin reduced not only LPC-induced cell death but also lactate dehydrogenase (LDH) leakage. Luteolin inhibition of LPC-induced apoptosis in endothelial cells demonstrated its protection against the cytotoxicity of LPC. LPC-induced apoptosis is characterized by a calcium-dependent mitochondrial pathway, involving calcium influx, activation of calpains, cytochrome C release and caspases activation. Luteolin reduced calcium influx. It also inhibited calpains activation and prevented the release of cytochrome C from mitochondrion. The inhibition of cytochrome C release by luteolin blocked the activation of caspase-3 and thus prevented subsequent endothelial cell apoptosis. These results suggested that luteolin inhibits LPC-induced apoptosis in endothelial cells through the blockage of the calcium-dependent mitochondrial pathway.
Song
Junna
J
Department of Pharmacology of Chinese Materia Medica, Chinese Pharmaceutical University, Nainjing, PR China.
Liu
Kang
K
Yi
Jiali
J
Zhu
Deqiu
D
Liu
Gaolin
G
Liu
Baolin
B
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002154:Calpain / Q000037:antagonists & inhibitors / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000188:drug therapy; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D047311:Luteolin / Q000494:pharmacology*; D008244:Lysophosphatidylcholines / Q000037:antagonists & inhibitors* / Q000633:toxicity; D053858:Metabolic Networks and Pathways / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism
D061945:Caspase Inhibitors; D008244:Lysophosphatidylcholines; D007770:L-Lactate Dehydrogenase; D002154:Calpain; D020169:Caspases; D047311:Luteolin; D002118:Calcium