PbAc Triggers Oxidation and Apoptosis Via the PKA Pathway in NRK-52E Cells

Overview

Journal Biol Trace Elem Res

Date 2020 Sep 14

PMID 32926327

Authors

Duanya Liu

Jun Yu

Jie Xie

Zhaoyu Zhang

Caoli Tang

Tianmei Yu

Shouni Chen

Zhidan Hong

Chunhong Wang

Affiliations

Soon will be listed here.

Abstract

This study aimed to investigate the mechanism of the lead exposure-induced oxidative stress and apoptosis of renal tubular epithelial cells. We explored the effects of lead acetate (PbAc) on the oxidation and apoptosis of renal proximal tubular cells (NRK-52E) through in vitro experiments. Results showed that PbAc induced dose-dependent reactive oxygen species (ROS) accumulation in NRK-52E cells, and the activities of superoxide dismutase (SOD) and glutathione (GSH) decreased, whereas the malondialdehyde (MDA) content increased. Under the exposure of 40 and 80 μM PbAc, the mRNA level of B cell lymphoma-2 (Bcl-2) in the cells decreased, the mRNA levels of Bcl-2-associated X protein (Bax) and caspase-3 increased, and apoptosis was obvious. Furthermore, the nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4) activity was enhanced by PbAc in a dose-dependent manner. The mRNA levels of protein kinase A (PKA) were upregulated by PbAc. H-89, a PKA inhibitor, suppressed PKA activation, ROS accumulation, and Nox4 activity in NRK-52E cells. Our results indicated that PbAc potentially stimulated oxidative stress and apoptosis in NRK-52E cells by increasing Nox4-dependent ROS production via the PKA signaling pathway.

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