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.

中文翻译：

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PbAc 通过 NRK-52E 细胞中的 PKA 途径触发氧化和细胞凋亡。

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）对肾近端肾小管细胞（NRK-52E）氧化和凋亡的影响。结果表明，PbAc 在 NRK-52E 细胞中诱导剂量依赖性活性氧 (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40和80 μM PbAc作用下，细胞内B细胞淋巴瘤-2（Bcl-2）mRNA水平降低，Bcl-2相关X蛋白（Bax）和caspase-3 mRNA水平升高，凋亡明显。此外，PbAc 以剂量依赖性方式增强了烟酰胺腺嘌呤二核苷酸磷酸氧化酶 4 (Nox4) 的活性。蛋白激酶 A (PKA) 的 mRNA 水平被 PbAc 上调。H-89 是一种 PKA 抑制剂，可抑制 NRK-52E 细胞中的 PKA 活化、ROS 积累和 Nox4 活性。我们的结果表明，PbAc 可能通过 PKA 信号通路增加 Nox4 依赖性 ROS 的产生，从而刺激 NRK-52E 细胞的氧化应激和细胞凋亡。