Modulation of nonselective cation current by oxidized LDL and lysophosphatidylcholine and its inhibitory contribution to endothelial damage

Guo Hua Liang, Seonghee Park, Moon Young Kim, Ji Aee Kim, Shinkyu Choi, Suk-Hyo Suh

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Aims: This study examined the effects of oxidized low-density lipoprotein (LDL) and its major lipid constituent lysophosphatidylcholine (LPC) on nonselective cation (NSC) current and its inhibitory contribution to LPC-induced cytotoxicity in cultured human umbilical endothelial cells (HUVECs). Main methods: Patch-clamp technique and the resazurin-based cell viability assay were used. Key findings: In voltage-clamped cells, oxidized LDL or LPC slowly activated NSC current. NSC current was also activated by loading cells with Ca2+ solution buffered at various concentrations using a patch pipette or by applying the sarcoplasmic reticulum Ca2+ pump blocker 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ), the metabolic inhibitor CN- or the hydroperoxide donor tert-butyl hydroperoxide (TBHP). On the contrary, when intracellular Ca2+ was strongly buffered with 12mM BAPTA or cells were loaded with superoxide dismutase using a patch pipette, LPC or BHQ did not activate NSC current. Furthermore, NSC current activated by LPC, TBHP or CN- was inhibited by the antioxidant tempol or extracellular Ca2+ depletion and NSC current activated by intracellular Ca2+ was further augmented by oxidized LDL or LPC. LPC or oxidized LDL released Ca2+ from intracellular stores and further enhanced store-operated Ca2+ entry. LPC-induced cytotoxicity was augmented by inhibiting Ca2+ influx and NO synthesis. Significance: Oxidized LDL or its main component LPC activated Ca2+-permeable NSC current via releasing Ca2+ from intracellular stores and producing ROS and thereby increased Ca2+ influx. Ca2+ influx through NSC channel might protect endothelial cells by producing NO.

Original languageEnglish
Pages (from-to)733-739
Number of pages7
JournalLife Sciences
Volume86
Issue number19-20
DOIs
StatePublished - May 2010

Bibliographical note

Funding Information:
This work was supported by the Korea Research Foundation Grant funded by the Korea Government (MOEHRD) ( KRF-2006-041-E00014 ).

Keywords

  • Ca entry
  • Endothelial cell
  • Lysophosphatidylcholine
  • Nonselective cation current
  • Oxidized LDL

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