Lead inhibits paraoxonase 2 but not paraoxonase 1 activity in human hepatoma HepG2 cells

Abstract

Lead is an environmental toxicant of great concern for humans and animals. Lead-induced liver damage and malfunction are partly due to a disturbance of the cellular antioxidant balance. Paraoxonase 1 (PON1) and PON2 are highly expressed in the liver and have been proposed as antioxidative enzymes. In this study, the effects of lead on PON1 and PON2 activities were investigated in human hepatoma HepG2 cells by exposing the cells to various concentrations of lead acetate for 24, 48, or 72 h. The results show that a significant increase in reactive oxygen species was observed even at the lowest concentration of lead treatment. However, only the highest concentration of lead significantly influenced cell viability. Lead had no influence on cell-associated PON1 activity, but it significantly decreased cytoplasmic PON2 activity in a concentration- and time-dependent manner. This reduction was rescued by the addition of calcium. A significant increase of PON2 transcript was observed by real-time polymerase chain reaction, while PON2 protein expression did not change in the western blot analysis. Taken together, these results indicate that lead reduces PON2, but not PON1, activity and that this reduction is reversed by calcium. Lead-induced oxidative stress and decreased PON2 activity lead to the upregulation of PON2 transcript.

Protective Effect of Opuntia dillenii Haw Fruit against Lead Acetate-Induced Hepatotoxicity: In Vitro and In Vivo Studies

“…Furthermore, another design was also done to evaluate the extract's protective impact on lead acetate-induced cell death. In review, the cells were pretreated at concentrations of 0–80 μ g/ml for 24 hours and then subjected to 100 μ g/ml of lead acetate [ 44 ] for a further 24 hours of coincubation. Afterward, 10 μ l of MTT reagent (5 mg/ml) was added to each well incubated for the next 3 hours.…”

RHOA G17V induces T follicular helper cell specification and involves angioimmunoblastic T-cell lymphoma via upregulating the expression of PON2 through an NF-κB-dependent mechanism

“…Despite the established and dominant role of paraoxonases in cardiovascular diseases and relevant parameters, more recent studies revealed antioxidant and antiapoptotic activities of PON2 in cancers. 18 , 35 Several studies have indicated that PON2 is commonly upregulated in several tumor types, including pancreatic cancer, 20 , 36 hepatocellular carcinoma (HCC), 37 skin neoplasm, 21 , 38 prostate cancer, 39 and acute lymphoblastic leukemia. 40 , 41 A study reported that PON2 promotes cancer growth and metastasis in pancreatic cells by increasing cellular glucose uptake by modulating the GLUT1-mediated transport.…”

A carboxylesterase-selective ratiometric fluorescent two-photon probe and its application to hepatocytes and liver tissues

“…Centrifugation of the homogenate at 10 000 rpm for 15 min gave a clear supernatant which was collected into a new tube. 100 μg protein of the supernatant was incubated with 10 μM of each inhibitor (donepezil hydrochloride monohydrate for the AChE inhibitor, 45 ethopropazine hydrochloride for the BChE inhibitor, 46 naringenin for the PON1 inhibitor, 47 lead acetate for the PON2 inhibitor, 48 and bis(4-nitrophenyl) phosphate (BNPP) for the CE inhibitor). 37 The relative fluorescence intensity of 3 μM SE1 with each inhibitor was acquired after 15 min incubation.…”