Luteolin inhibits lysophosphatidylcholine-induced apoptosis in endothelial cells by a calcium/mitocondrion/caspases-dependent pathway

Planta Med. 2010 Mar;76(5):433-8. doi: 10.1055/s-0029-1186197. Epub 2009 Oct 14.

Abstract

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.

MeSH terms

  • Apoptosis / drug effects*
  • Calcium / metabolism
  • Calpain / antagonists & inhibitors
  • Calpain / metabolism
  • Cardiovascular Diseases / drug therapy
  • Caspase Inhibitors
  • Caspases / metabolism
  • Endothelial Cells / drug effects*
  • Endothelial Cells / metabolism
  • Enzyme Activation / drug effects
  • Humans
  • L-Lactate Dehydrogenase / metabolism
  • Luteolin / pharmacology*
  • Lysophosphatidylcholines / antagonists & inhibitors*
  • Lysophosphatidylcholines / toxicity
  • Metabolic Networks and Pathways / drug effects
  • Mitochondria / metabolism

Substances

  • Caspase Inhibitors
  • Lysophosphatidylcholines
  • L-Lactate Dehydrogenase
  • Calpain
  • Caspases
  • Luteolin
  • Calcium