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

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.

Oxidized Low Density Lipoprotein Induces Bone Morphogenetic Protein-2 in Coronary Artery Endothelial Cells via Toll-like Receptors 2 and 4

“…Together, these results demonstrate that oxLDL up-regulates BMP-2 production in human CAECs through a mechanism dependent on TLR2 and TLR4. In this regard, cell death in dorsal root ganglion cell culture induced by oxLDL is attributed to TLR4, not LOX-1 (16). Our further experiments using immunostaining found that oxLDL is co-localized with TLR2 and TLR4.…”

“…Interestingly, minimally modified LDL induces macrophage actin polymerization and cell spreading via a TLR4-dependent mechanism (14). Further, oxLDL induces cell death in ganglion culture in a TLR4-dependent fashion (16). These studies indicate a role for TLR4 in mediating the effect of oxLDL.…”

Activation of Macrophages by P2X7-Induced Microvesicles from Myeloid Cells Is Mediated by Phospholipids and Is Partially Dependent on TLR4

“…Recently, it was demonstrated that oxidized low density lipoprotein (oxLDL), which bind to the scavenger receptor B family member CD36, can promote sterile inflammation through activation of TLR4/6 heterodimer on macrophages (56). Both cell death (57, 58) and foam-cell formation (59) have also been shown to be induced by oxidized LDL through TLR4 in macrophages. Furthermore, oxidized phospholipids from minimally modified low density lipoprotein (mmLDL), which contain essentially the same phospholipids as oxLDL, stimulate macrophage ROS generation (60), ERK activation (61), membrane spreading (62), and inhibition of phagocytic uptake of apoptotic bodies (62), through a partially TLR4-dependent pathway.…”

Leptin-deficient (ob/ob) mouse ovaries show fatty degeneration, enhanced apoptosis and decreased expression of steroidogenic acute regulatory enzyme

“…15,18 The oxidised lipoproteinsdependent activation of these receptors either triggers apoptosis or survival autophagy in endothelial or granulosa cells. 14,18,19 Ob/ob ovaries could respond to lipid droplet accumulation by upregulation of LOX-1 and/or TLR4 resulting in the cell damage. If so, follicular atresia is not because of leptin-deficiency only.…”