Department of Preventive Medicine, School of Health Sciences, Wuhan University, Wuhan, 430071, People's Republic of China.
Reproductive Medicine Center, Zhongnan Hospital of Wuhan University, Wuhan, 430071, People's Republic of China.
Biol Trace Elem Res. 2021 Jul;199(7):2687-2694. doi: 10.1007/s12011-020-02378-3. Epub 2020 Sep 14.
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.
本研究旨在探讨铅暴露诱导肾小管上皮细胞氧化应激和凋亡的机制。我们通过体外实验探讨了醋酸铅（PbAc）对肾近端小管细胞（NRK-52E）氧化和凋亡的影响。结果表明，PbAc 诱导 NRK-52E 细胞中依赖剂量的活性氧（ROS）积累，超氧化物歧化酶（SOD）和谷胱甘肽（GSH）的活性降低，而丙二醛（MDA）含量增加。在暴露于 40 和 80 μM PbAc 下，细胞中 B 细胞淋巴瘤-2（Bcl-2）的 mRNA 水平降低，Bcl-2 相关 X 蛋白（Bax）和半胱天冬酶-3（caspase-3）的 mRNA 水平升高，细胞凋亡明显。此外，PbAc 以剂量依赖的方式增强烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4（Nox4）的活性。PbAc 上调蛋白激酶 A（PKA）的 mRNA 水平。PKA 抑制剂 H-89 抑制了 NRK-52E 细胞中 PKA 的激活、ROS 的积累和 Nox4 的活性。我们的结果表明，PbAc 通过增加 PKA 信号通路中依赖 Nox4 的 ROS 产生，潜在地刺激 NRK-52E 细胞中的氧化应激和凋亡。
