Lipopolysaccharide induces endothelial cell apoptosis via activation of Na(+)/H(+) exchanger 1 and calpain-dependent degradation of Bcl-2

Biochem Biophys Res Commun. 2012 Oct 12;427(1):125-32. doi: 10.1016/j.bbrc.2012.09.023. Epub 2012 Sep 17.

Abstract

The calcium-dependent protease calpain is involved in lipopolysaccharide (LPS)-induced endothelial injury. The activation of Na(+)/H(+) exchanger (NHE) is responsible to increase intracellular Ca(2+) (Ca(i)(2+)) in cardiovascular diseases. Here we hypothesized that activation of NHE mediates LPS-induced endothelial cell apoptosis via calcium-dependent calpain pathway. Our results revealed that LPS-induced increases in NHE activity are dependent on NHE1 in human umbilical vein endothelial cells (HUVECs). Treatment of HUVECs with LPS increased the NHE1 activity in a time-dependent manner associated with the increased Ca(i)(2+), which resulted in enhanced calpain activity as well as HUVECs apoptosis via NHE1-dependent degradation of Bcl-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / immunology*
  • Calcium / metabolism
  • Calpain / metabolism*
  • Cation Transport Proteins / biosynthesis*
  • Cells, Cultured
  • Human Umbilical Vein Endothelial Cells / immunology*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Lipopolysaccharides / immunology*
  • Proteolysis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers / biosynthesis*

Substances

  • Cation Transport Proteins
  • Lipopolysaccharides
  • Proto-Oncogene Proteins c-bcl-2
  • SLC9A1 protein, human
  • Sodium-Hydrogen Exchanger 1
  • Sodium-Hydrogen Exchangers
  • Calpain
  • Calcium