Wei Zejing, Nie Gaohui, Yang Fan, Pi Shaoxing, Wang Chang, Cao Huabin, Guo Xiaoquan, Liu Ping, Li Guyue, Hu Guoliang, Zhang Caiying
Jiangxi Provincial Key Laboratory for Animal Health, Institute of Animal Population Health, College of Animal Science and Technology, Jiangxi Agricultural University, No. 1101 Zhimin Avenue, Economic and Technological Development District, Nanchang, 330045, Jiangxi, PR China.
School of Information Technology, Jiangxi University of Finance and Economics, No. 665 Yuping West Street, Economic and Technological Development District, Nanchang, 330032, Jiangxi, PR China.
Environ Pollut. 2020 Oct 23;273:115919. doi: 10.1016/j.envpol.2020.115919.
Cadmium (Cd) is an occupational and environmental pollutant, which mainly causes nephrotoxicity by damaging renal proximal tubular cells. To evaluate the effects of Cd on pyroptosis and the relationship between pyroptosis and apoptosis in duck renal tubular epithelial cells, the cells were cultured with 3CdSO·8HO (0, 2.5, 5.0, or 10.0 μM Cd), N-acetyl-L-cysteine (NAC) (100.0 μM), Z-YVAD-FMK (10.0 μM) or the combination of Cd and NAC or Z-YVAD-FMK for 12 h, and then cytotoxicity was assessed. The results evidenced that Cd significantly increased the releases of interleukin-18 (IL-18) and interleukin-1β (IL-1β), lactate dehydrogenase (LDH) and nitric oxide (NO), relative conductivity and cellular reactive oxygen species (ROS) level. Simultaneously, Cd also markedly upregulated NLRP3, Caspase-1, ASC, NEK7, IL-1β and IL-18 mRNA levels and NLRP3, Caspase-1 p20, GSDMD and ASC protein levels. Additionally, NAC notably improved the changes of above indicators induced by Cd. Combined treatment with Cd and Z-YVAD-FMK remarkably elevated Bcl-2 mRNA and protein levels, inhibited p53, Bax, Bak-1, Cyt C, Caspase-9 and Caspase-3 mRNA levels and p53, Bax, Bak-1, Caspase-9/cleaved Caspase-9 and Caspase-3/cleaved Caspase-3 protein levels, increased mitochondrial membrane potential (MMP), decreased apoptosis ratio and cell damage compared to treatment with Cd alone. Taken together, Cd exposure induces duck renal tubular epithelial cell pyroptosis through ROS/NLRP3/Caspase-1 signaling pathway, and inhibiting Caspase-1 dependent pyroptosis attenuates Cd-induced apoptosis.
镉（Cd）是一种职业和环境污染物，主要通过损伤肾近端小管细胞而导致肾毒性。为了评估镉对鸭肾小管上皮细胞焦亡的影响以及焦亡与凋亡之间的关系，将细胞分别用3CdSO·8HO（0、2.5、5.0或10.0 μM镉）、N-乙酰-L-半胱氨酸（NAC）（100.0 μM）、Z-YVAD-FMK（10.0 μM）或镉与NAC或Z-YVAD-FMK的组合处理12小时，然后评估细胞毒性。结果表明，镉显著增加了白细胞介素-18（IL-18）、白细胞介素-1β（IL-1β）、乳酸脱氢酶（LDH）、一氧化氮（NO）的释放、相对电导率和细胞活性氧（ROS）水平。同时，镉还显著上调了NLRP3、半胱天冬酶-1（Caspase-1）、凋亡相关斑点样蛋白（ASC）、NEK7、IL-1β和IL-18的mRNA水平以及NLRP3、Caspase-1 p20、Gasdermin D（GSDMD）和ASC的蛋白水平。此外，NAC显著改善了镉诱导的上述指标变化。与单独用镉处理相比，镉与Z-YVAD-FMK联合处理显著提高了Bcl-2的mRNA和蛋白水平，抑制了p53、Bax、Bak-1、细胞色素C（Cyt C）、Caspase-9和Caspase-3的mRNA水平以及p53、Bax、Bak-1、Caspase-9/切割的Caspase-9和Caspase-3/切割的Caspase-3的蛋白水平，增加了线粒体膜电位（MMP），降低了凋亡率和细胞损伤。综上所述，镉暴露通过ROS/NLRP3/Caspase-1信号通路诱导鸭肾小管上皮细胞焦亡，抑制Caspase-1依赖性焦亡可减轻镉诱导的凋亡。
