Ascorbate does not protect macrophages against apoptosis induced by oxidised low density lipoprotein

Abstract

Apoptosis of macrophages and smooth muscle cells is observed in atherosclerotic lesions and may play an important role in the disease progression. Oxidised low density lipoprotein (LDL) is cytotoxic and induces apoptosis in a variety of cell types. We reported previously that ascorbate protects arterial smooth muscle cells from apoptosis induced by oxidised LDL containing the peak levels of lipid hydroperoxides. We now demonstrate that macrophages undergo apoptosis when treated with this species of oxidised LDL, as detected by increased annexin V binding and DNA fragmentation. Ascorbate treatment of macrophages did not protect against the cytotoxicity of oxidised LDL, and modestly increased the levels of annexin V binding and DNA fragmentation. Oxidised LDL treatment also increased the expression of the antioxidant stress protein heme oxygenase-1 in macrophages; however, this increase was markedly attenuated by ascorbate pretreatment. Although apoptosis induced by oxidised LDL was modestly promoted by ascorbate, ascorbate apparently decreased the levels of oxidative stress in macrophages, suggesting that this pro-apoptotic effect was not mediated by a pro-oxidant mechanism, but may instead have been due to intracellular protection of the apoptotic machinery by ascorbate.

Cadmium-induced heme oxygenase-1 gene expression is associated with the depletion of glutathione in the roots of Medicago sativa

“…These findings are consistent with those reported by Yannarelli et al (2006), in which they found that AsA pretreatment prevented the UV-Binduced up-regulation of HO-1 mRNA in soybean plants. Similar effects of AsA on HO-1 gene expression were also confirmed in animals subjected to oxidized low density lipoprotein (LDL), Cd, chromium (Cr) treatments (Harris et al 2006;Elbekai et al 2007). For example, pretreatment of smooth muscle cells (SMC) with the antioxidant vitamin C attenuated the induction of HO-1 by moderately oxidized LDL (moxLDL) or highly oxidized LDL (oxLDL) compared with cells not pretreated with vitamin C (Anwar et al 2005).…”

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

“…9 -15,21-25,32,33 Almost all of these studies have shown adverse effect of oxLDL, including cell apoptosis and death. 11,12,24,32,33 Unfortunately, the concentration of oxLDL used in these studies has varied from 10 to 100 g/mL. Although the precise concentration of oxLDL in the tissues is not known, these concentrations are at least 1-log higher than those seen in normal human sera.…”

Mechanism of the antioxidant to pro-oxidant switch in the behavior of dehydroascorbate during LDL oxidation by copper(II) ions

“…LDL (150 µg protein/ml) was oxidised at 37°C by adding CuSO 4 (5 µM net above the calculated final EDTA concentration) in PBS, as described previously [58]. Briefly, the initial absorbance at 234 nm was read and further readings were taken every 15-20 min.…”