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

被引：0
作者：
Duanya Liu
Jun Yu
Jie Xie
Zhaoyu Zhang
Caoli Tang
Tianmei Yu
Shouni Chen
Zhidan Hong
Chunhong Wang
机构：
[1] Wuhan University,Department of Preventive Medicine, School of Health Sciences
[2] Zhongnan Hospital of Wuhan University,Reproductive Medicine Center
来源：
Biological Trace Element Research | 2021年 / 199卷
关键词：
PbAc; Tubular cells; Oxidative stress; PKA; Nox4;
D O I：
暂无
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学科分类号：
摘要：
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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页码：2687 / 2694
页数：7
相关论文
共 149 条
[1]  
Nakhaee S(2019)Impact of chronic lead exposure on liver and kidney function and haematologic parameters Basic Clin Pharmacol Toxicol 124 621-628
[2]  
Amirabadizadeh A(2016)Lead exposure and oxidative stress: a systematic review Rev Environ Contam Toxicol 236 193-238
[3]  
Brent J(2011)Advances in metal-induced oxidative stress and human disease Toxicology 283 65-87
[4]  
Mehrpour O(2004)Direct interaction of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase J Biol Chem 279 45935-45941
[5]  
Lopes AC(2016)Role of NADPH oxidase in metabolic disease-related renal injury: an update Oxidative Med Cell Longev 2016 7813072-20382
[6]  
Peixe TS(2019)Mitochondrial biogenesis and mitochondrial reactive oxygen species (ROS): a complex relationship regulated by the cAMP/PKA signaling pathway Cells 8 287-2076
[7]  
Mesas AE(2006)cAMP-response element-binding protein mediates acid-induced NADPH oxidase NOX5-S expression in Barrett esophageal adenocarcinoma cells J Biol Chem 281 20368-C692
[8]  
Paoliello MM(2011)Vasoactive intestinal peptide reduces oxidative stress in pancreatic acinar cells through the inhibition of NADPH oxidase Peptides 32 2067-9446
[9]  
Jomova K(2019)G protein-coupled estrogen receptor protects from angiotensin II-induced increases in pulse pressure and oxidative stress Front Endocrinol (Lausanne) 10 586-409
[10]  
Valko M(2013)CREB, NF-κB, and NADPH oxidase coordinately upregulate indoxyl sulfate-induced angiotensinogen expression in proximal tubular cells Am J Physiol Cell Physiol 304 C685-582
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