Biochemical and Biophysical Research Communications, Vol.427, No.1, 125-132, 2012
Lipopolysaccharide induces endothelial cell apoptosis via activation of Na+/H+ exchanger 1 and calpain-dependent degradation of Bcl-2
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 Ca2+ (Ca-j(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-j(2+), which resulted in enhanced calpain activity as well as HUVECs apoptosis via NHE1-dependent degradation of Bcl-2. (C) 2012 Elsevier Inc. All rights reserved.