Ziqi Ren , Yuanchen Zheng , Jianli Liu , Zhicun Liu , Jiahe Chen , Haotian Liu , Ruiquan Qi , Huiping Ma
{"title":"镉诱导HEK293细胞分泌受MAPK和NF-κB信号通路调控的SASP因子:镉致急性肾损伤的可能机制","authors":"Ziqi Ren , Yuanchen Zheng , Jianli Liu , Zhicun Liu , Jiahe Chen , Haotian Liu , Ruiquan Qi , Huiping Ma","doi":"10.1016/j.tox.2025.154166","DOIUrl":null,"url":null,"abstract":"<div><div>Cadmium (Cd) is a highly toxic environmental pollutant, which can accumulate in the kidney, induce cell damage and trigger inflammatory responses. However, the specific regulation mechanism of nephrotoxicity induced by Cd remains unclear. This study was conducted to investigate the toxic effects of Cd on human embryonic kidney 293 (HEK293) cells and explore its potential mechanisms. Cell viability was assessed with MTT assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated through DCFH-DA staining and Rhodamine staining. Apoptosis was detected with Hoechst 33258 staining. The expression of the DNA damage biomarker 8-hydroxy-2’-deoxyguanosine (8-OHdG) was detected with the 8-OHdG ELISA kit. Senescence-associated secretory phenotype (SASP) factors and signaling pathways were analyzed by Western blot. The results showed that Cd exposure could induce oxidative stress and cellular inflammation. It could also impair MMP, contribute to cell apoptosis and activate MAPK and NF-κB signaling pathways. Finally, exposure to Cd triggered DNA damage and SASP production. However, NF-κB inhibitor BAY11–7082 and antioxidant NAC could inhibit these effects by suppressing NF-κB and MAPK signaling pathways. The present study revealed the specific mechanisms of Cd toxicity in HEK293 cells and provided useful information for elucidating the nephrotoxicity of Cd.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":"515 ","pages":"Article 154166"},"PeriodicalIF":4.8000,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cadmium induces the secretion of SASP factors regulated by MAPK and NF-κB signaling pathways in HEK293 cells: A possible mechanism of acute kidney damage induced by cadmium\",\"authors\":\"Ziqi Ren , Yuanchen Zheng , Jianli Liu , Zhicun Liu , Jiahe Chen , Haotian Liu , Ruiquan Qi , Huiping Ma\",\"doi\":\"10.1016/j.tox.2025.154166\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Cadmium (Cd) is a highly toxic environmental pollutant, which can accumulate in the kidney, induce cell damage and trigger inflammatory responses. However, the specific regulation mechanism of nephrotoxicity induced by Cd remains unclear. This study was conducted to investigate the toxic effects of Cd on human embryonic kidney 293 (HEK293) cells and explore its potential mechanisms. Cell viability was assessed with MTT assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated through DCFH-DA staining and Rhodamine staining. Apoptosis was detected with Hoechst 33258 staining. The expression of the DNA damage biomarker 8-hydroxy-2’-deoxyguanosine (8-OHdG) was detected with the 8-OHdG ELISA kit. Senescence-associated secretory phenotype (SASP) factors and signaling pathways were analyzed by Western blot. The results showed that Cd exposure could induce oxidative stress and cellular inflammation. It could also impair MMP, contribute to cell apoptosis and activate MAPK and NF-κB signaling pathways. Finally, exposure to Cd triggered DNA damage and SASP production. However, NF-κB inhibitor BAY11–7082 and antioxidant NAC could inhibit these effects by suppressing NF-κB and MAPK signaling pathways. The present study revealed the specific mechanisms of Cd toxicity in HEK293 cells and provided useful information for elucidating the nephrotoxicity of Cd.</div></div>\",\"PeriodicalId\":23159,\"journal\":{\"name\":\"Toxicology\",\"volume\":\"515 \",\"pages\":\"Article 154166\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0300483X25001234\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0300483X25001234","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
Cadmium induces the secretion of SASP factors regulated by MAPK and NF-κB signaling pathways in HEK293 cells: A possible mechanism of acute kidney damage induced by cadmium
Cadmium (Cd) is a highly toxic environmental pollutant, which can accumulate in the kidney, induce cell damage and trigger inflammatory responses. However, the specific regulation mechanism of nephrotoxicity induced by Cd remains unclear. This study was conducted to investigate the toxic effects of Cd on human embryonic kidney 293 (HEK293) cells and explore its potential mechanisms. Cell viability was assessed with MTT assay. Reactive oxygen species (ROS) levels and mitochondrial membrane potential (MMP) were evaluated through DCFH-DA staining and Rhodamine staining. Apoptosis was detected with Hoechst 33258 staining. The expression of the DNA damage biomarker 8-hydroxy-2’-deoxyguanosine (8-OHdG) was detected with the 8-OHdG ELISA kit. Senescence-associated secretory phenotype (SASP) factors and signaling pathways were analyzed by Western blot. The results showed that Cd exposure could induce oxidative stress and cellular inflammation. It could also impair MMP, contribute to cell apoptosis and activate MAPK and NF-κB signaling pathways. Finally, exposure to Cd triggered DNA damage and SASP production. However, NF-κB inhibitor BAY11–7082 and antioxidant NAC could inhibit these effects by suppressing NF-κB and MAPK signaling pathways. The present study revealed the specific mechanisms of Cd toxicity in HEK293 cells and provided useful information for elucidating the nephrotoxicity of Cd.
期刊介绍:
Toxicology is an international, peer-reviewed journal that publishes only the highest quality original scientific research and critical reviews describing hypothesis-based investigations into mechanisms of toxicity associated with exposures to xenobiotic chemicals, particularly as it relates to human health. In this respect "mechanisms" is defined on both the macro (e.g. physiological, biological, kinetic, species, sex, etc.) and molecular (genomic, transcriptomic, metabolic, etc.) scale. Emphasis is placed on findings that identify novel hazards and that can be extrapolated to exposures and mechanisms that are relevant to estimating human risk. Toxicology also publishes brief communications, personal commentaries and opinion articles, as well as concise expert reviews on contemporary topics. All research and review articles published in Toxicology are subject to rigorous peer review. Authors are asked to contact the Editor-in-Chief prior to submitting review articles or commentaries for consideration for publication in Toxicology.