Lysophosphatidylcholine-induced cytotoxicity and protection by heparin in mouse brain bEND.3 endothelial cells

Tien Yao Tsai, Iat Lon Leong, Ka Shun Cheng, Lian Ru Shiao, Tzu Hui Su, Kar Lok Wong, Paul Chan, Yuk Man Leung

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

A pathological feature in atherosclerosis is the dysfunction and death of vascular endothelial cells (EC). Oxidized low-density lipoprotein (LDL), known to accumulate in the atherosclerotic arterial walls, impairs endothelium-dependent relaxation and causes EC apoptosis. A major bioactive ingredient of the oxidized LDL is lysophosphatidylcholine (LPC), which at higher concentrations causes apoptosis and necrosis in various EC. There is hitherto no report on LPC-induced cytotoxicity in brain EC. In this work, we found that LPC caused cytosolic Ca 2+ overload, mitochondrial membrane potential decrease, p38 activation, caspase 3 activation and eventually apoptotic death in mouse cerebral bEND.3 EC. In contrast to reported reactive oxygen species (ROS) generation by LPC in other EC, LPC did not trigger ROS formation in bEND.3 cells. Pharmacological inhibition of p38 alleviated LPC-inflicted cell death. We examined whether heparin could be cytoprotective: although it could not suppress LPC-triggered Ca 2+ signal, p38 activation and mitochondrial membrane potential drop, it did suppress LPC-induced caspase 3 activation and alleviate LPC-inflicted cytotoxicity. Our data suggest LPC apoptotic death mechanisms in bEND.3 might involve mitochondrial membrane potential decrease and p38 activation. Heparin is protective against LPC cytotoxicity and might intervene steps between mitochondrial membrane potential drop/p38 activation and caspase 3 activation.

Original languageEnglish
Pages (from-to)52-62
Number of pages11
JournalFundamental and Clinical Pharmacology
Volume33
Issue number1
DOIs
Publication statusPublished - Feb 1 2019

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Keywords

  • apoptosis
  • atherosclerosis
  • endothelial cells
  • heparin
  • lysophosphatidylcholine

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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