Cadmium induces ferroptosis by modulating Nrf2/HO-1 pathway in PK-15 cells
10.16303/j.cnki.1005-4545.2024.09.19
- VernacularTitle:镉通过Nrf2/HO-1通路诱导猪肾PK-15细胞铁死亡
- Author:
Shengzhe SONG
1
;
Tongwang LUO
;
Lingjun SHEN
;
Ya WU
;
Shujie WANG
;
Xiaoqiang YU
;
Houhui SONG
;
Chunyan SHAO
Author Information
1. 浙江农林大学动物科技学院/动物医学院浙江省畜禽绿色生态健康养殖应用技术研究重点实验室/动物健康互联网检测技术浙江省工程实验室,动物医学与健康管理浙江省国际科技合作基地/中澳动物健康大数据分析联合实验室,浙江 杭州 311300
- Keywords:
cadmium;
PK-15;
HO-1;
ferroptosis
- From:
Chinese Journal of Veterinary Science
2024;44(9):1992-1998
- CountryChina
- Language:Chinese
-
Abstract:
Cadmium is a non-essential,non-degradable heavy metal element,the accumulation of cadmium can cause kidney damage.The purpose of this study was to reveal the ferroptosis mecha-nism induced by cadmium exposure in porcine kidney PK-15 cells.First of all,cell viability of gradi-ent concentration of cadmium chloride(CdCl2)on PK-15 cells was detected by CCK-8 method to screen suitable work concentration of CdCl2.Secondly,PK-15 cells were treated with 10 μmol/L CdCl2 for 3,6 and 12 h.The contents of lactate dehydrogenase(LDH)malondialdehyde(MDA)were detected by colorimetry,the expression of ferroptosis related protein were detected by West-ern blot,and the content of ferrous ion(Fe2+)was detected by fluorescence probe.Finally,PK-15 cells were pretreated with 10 μmol/L HO-1 inhibitor zinc protoporphyrin(ZnPP)for 6 h,and then treated with 10 μmol/L CdCl2 for 12 h.The morphology of PK-15 cells was observed by phase contrast microscope and the expression of ferroptosis related proteins was detected by West-ern blot.The results showed that CdCl2 treatment caused a significant decrease in cell viability.The levels of LDH,MDA and Fe2+,the protein levels of Nrf2,HO-1 and ALOX5,and the expression level of FTH1 protein were significantly decreased in CdCl2 treatment cells(P＜0.01).ZnPP could significantly improve the ferroptosis of PK-15 cells induced by CdCl2 treatment.Compared with CdCl2 treatment cells,the cell morphology was significantly improved,the protein levels of Nrf2,HO-1 and ALOX5 protein were significantly decreased,and the protein levels of FTH1 protein were significantly increased in ZnPP pretreatment group(P＜0.01).The results showed that cad-mium induced iron overload and lipid peroxidation,which result in ferroptosis in PK-15 cells through Nrf2/HO-1 pathway.
