Oxidized low-density lipoprotein (oxLDL)-induced cell death in dorsal root ganglion cell cultures depends not on the lectin-like oxLDL receptor-1 but on the toll-like receptor-4

J Neurosci Res. 2010 Feb 1;88(2):403-12. doi: 10.1002/jnr.22205.

Abstract

DRG cells have been found to undergo apoptosis and necrosis after oxidized low-density lipoprotein (oxLDL) stimulation in vitro. However, the mechanism of oxLDL-induced DRG cell death is unclear. For this reason, we studied the expression of two potential oxLDL receptors: lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) and toll-like receptor-4 (TLR4) in dorsal root ganglion (DRG) cell cultures from postnatal rats. Cells were cultivated with and without oxLDL. In oxLDL-treated DRG cell cultures, the increase of cleaved caspase-3 protein was observed as a sign of enhanced apoptosis. Untreated and oxLDL-treated DRG cell cultures expressed LOX-1 and TLR4 at similar levels. The LOX-1 expression remained unchanged after receptor blockade. However, the inhibition of LOX-1 caused a significant increase of cleaved caspase-3 and a decrease of TLR4 levels. The TLR4-inhibited DRG cell cultures lacked changes in LOX-1 expression for all experimental groups. The inhibition of TLR4 caused activation of jun N-terminal kinase (JNK) and a significant decrease of cleaved caspase-3 but did not change the TLR4 level. We conclude that LOX-1 and TLR4 are expressed in cultivated rat DRG cells and that the oxLDL-induced cell death in DRG cell cultures does not depend on the LOX-1 but on the TLR4.

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Caspase 3 / metabolism
  • Cell Death / physiology
  • Cells, Cultured
  • Ganglia, Spinal / physiology*
  • Ganglia, Spinal / ultrastructure
  • Lipoproteins, LDL / metabolism*
  • MAP Kinase Kinase 4 / metabolism
  • Male
  • Neurons / physiology*
  • Neurons / ultrastructure
  • Oxidation-Reduction
  • Rats
  • Rats, Inbred Strains
  • Scavenger Receptors, Class E / metabolism*
  • Toll-Like Receptor 4 / metabolism*

Substances

  • Lipoproteins, LDL
  • OLR1 protein, rat
  • Scavenger Receptors, Class E
  • Tlr4 protein, rat
  • Toll-Like Receptor 4
  • MAP Kinase Kinase 4
  • Casp3 protein, rat
  • Caspase 3