Iron–ascorbic acid‐induced oxidant stress and its quenching by paraoxonase 1 in HDL and the liver: Comparison between humans and rats

Abstract

Paraoxonase 1 (PON1) is a serum enzyme closely associated with high-density lipoprotein (HDL), which may protect against atherosclerosis by hydrolyzing lipid peroxides and several organophosphorus compounds. The purpose of the present study was to test the hypothesis that lipid peroxidation modifies the activity and protein mass of PON1 in humans and rats. Our findings revealed that the bulk of the activity monitored by the hydrolysis of paraoxon and phenyl acetate was confined to liver intracellular endoplasmic reticulum-derived microsomes and was mostly recovered in circulating HDL3. Confirmation was obtained by the determination of PON1 expression by Western blot. It is noteworthy that PON1 levels were consistently decreased in human sera, HDL, and liver microsomes compared with rat counterparts. Concomitant with iron-ascorbate-mediated lipid peroxidation, there was a decline in PON1 activity and protein in both HDL3 and microsomes, which was attenuated by butylated hydroxytoluene antioxidant treatment. The current data indicate that PON1 localization in microsomes and HDL3 could represent a selective cellular and lipoprotein response to oxidative stress. This was tested by the iron-ascorbate oxygen-radical generating system. It is also proposed that the increased PON1 level may have a function related to the well-known atherosclerosis resistance of rats.

CFTR silencing in pancreatic β-cells reveals a functional impact on glucose-stimulated insulin secretion and oxidative stress response

“…Of note, the iron dose used in the current study was moderate and comparable with normal iron concentrations in biological systems such as the gastrointestinal tract (2). We used Fe/Asc extensively as a strong oxygen radical-generating system in our previous studies (4,9,11,12,65,73). The data presented herein using MIN6 cells clearly indicate that the Fe/Asc system functions as a producer of lipid peroxidation, because the addition of the antioxidant Trolox simultaneously prevents the occurrence of lipid peroxidation and improves the cellular processes and functions.…”

Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases

“…Very recently, Trudel et al [33] observed a decrease of PON1 expression in human and rat livers in which an acute oxidant stress was produced by an iron-ascorbate oxygen-generating system. This suggests that PON1 response to acute insults and chronic diseases may be completely different.…”

Urokinase-Type Plasminogen Activator Downregulates Paraoxonase 1 Expression in Hepatocytes by Stimulating Peroxisome Proliferator–Activated Receptor-γ Nuclear Export

“…15 In contrast to PON2, PON1 protein expression and activity were shown to decrease under oxidative stress. 24,25 We thus hypothesized that increased oxidative stress in hepatocytes treated with uPA might subsequently be involved in the reduction in hepatocyte PON1 expression. Therefore, we next questioned whether uPA increases cellular oxidative stress in hepatocytes.…”