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.
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.
Nowicki
Marcin
M
Institute of Anatomy, University of Leipzig, Leipzig, Germany. marcin.nowicki@medizin.uni-leipzig.de
Müller
Kerstin
K
Serke
Heike
H
Kosacka
Joanna
J
Vilser
Constanze
C
Ricken
Albert
A
Spanel-Borowski
Katharina
K
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000502:physiology* / Q000648:ultrastructure; D008077:Lipoproteins, LDL / Q000378:metabolism*; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D051381:Rats; D011919:Rats, Inbred Strains; D051127:Scavenger Receptors, Class E / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
D008077:Lipoproteins, LDL; C495136:OLR1 protein, rat; D051127:Scavenger Receptors, Class E; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D048670:MAP Kinase Kinase 4; C505410:Casp3 protein, rat; D053148:Caspase 3