Oxidized lipoproteins activate NF-κB binding activity and apoptosis in PC12 cells

Abstract

Oxidative stress in the central nervous system may cause oxidation of lipoproteins. The oxidized lipoproteins may in turn damage cellular and subcellular membranes and other biomolecules, leading to tissue injury and cell death. Recently, we have demonstrated that oxidized LDL and VLDL induced cell death in a dose-dependent manner. The present study examined the possible signal transduction cascade leading to cell death by oxLDL and oxVLDL in PC12 cells. Using the electrophoretic mobility shift assay, we found that both oxLDL and oxVLDL activated the binding of NF-kappaB to the consensus sequence in the promoter region of the target genes, followed by apopototic cell death. Resveratrol protects the cells from both the activation of NF-kappa-B/ DNA binding activity and apoptotic cell death. Results indicated that oxidized lipoproteins may serve as an oxidative mediator and may activate apoptosis through a nuclear signalling pathway contributing to the pathology in Alzheimer's disease.

Resveratrol Modulates Phagocytosis of Bacteria through an NF-κB-Dependent Gene Program

“…The first evidence of resveratrol affecting NF-B was obtained by Draczynska-Lusiak et al (8). They demonstrated that oxidized lowdensity lipoprotein treatment activates NF-B in PC12 cells and that resveratrol attenuates the activation (8). Thereafter, there were many reports of resveratrol suppressing NF-B activation in a variety of cell lines, including U-937, Jurkat, and HeLa cells, induced by several agents, including 12-O-tetradecanoylphorbol-13-acetate, lipopolysaccharide, H 2 O 2 , and ceramide (4).…”

“…4 and 5). The first evidence of resveratrol affecting NF-B was obtained by Draczynska-Lusiak et al (8). They demonstrated that oxidized lowdensity lipoprotein treatment activates NF-B in PC12 cells and that resveratrol attenuates the activation (8).…”

Effects of resveratrol and methylprednisolone on biochemical, neurobehavioral and histopathological recovery after experimental spinal cord injury

“…Recently, resveratrol was found to be a highly potent antioxidant that could inhibit free radical generation in the brain, spinal cord, heart, kidney, liver, red cell membrane, and so on [19,36,[44][45][46][47][48][49] . It has been shown that it inhibits lipid peroxidation [50] , and prevents apoptotic cell death induced by oxidative stress [51,52] . It has been postulated that resveratrol could supress mitochondria-induced production of ROS in rat brain [53] , protect DNA from oxidative damage in stroke-prone hypertensive rats [54] , and could inhibit neuronal loss after ischemia/reperfusion injury in gerbils [44] .…”

Cardiovascular Protective Effects of Resveratrol

“…Apoptosis contributes to plaque instability, rupture and thrombus formation (61). Although it has not been proven in a vascular system, RSV (50 ìM) blocks apoptosis induced by oxidized VLDL and LDL in PC12 cells (21), and its antiapoptotic activity has been shown to depend on the direct inhibition of the main arachidonate metabolizing enzymes (58).…”