Lara Stoeberl , Madson Silveira de Melo , Letícia Cordeiro Koppe de França , Lorena Aparecida de Souza , Roberta de Cássia Panazzollo , Aline Pertile Remor , Viviane Glaser
{"title":"Assessing antioxidant responses in C6 and U-87 MG cell lines exposed to high copper levels","authors":"Lara Stoeberl , Madson Silveira de Melo , Letícia Cordeiro Koppe de França , Lorena Aparecida de Souza , Roberta de Cássia Panazzollo , Aline Pertile Remor , Viviane Glaser","doi":"10.1016/j.cbpc.2024.110065","DOIUrl":null,"url":null,"abstract":"<div><div>Copper excess has been tested as an anticancer therapy, due to its properties to generate oxidative stress resulting in tumoral cell death. Thus, this study aimed to evaluate the impact of copper excess on oxidative stress and antioxidant responses in glioma cells, establishing the antioxidant system as a target of copper toxicity in tumoral cells. C6 and U-87 MG cells were exposed to CuSO<sub>4</sub> (0–600 μM) for 24-48 h. SOD, CAT, GPx, GR, and CK activities, protein and non-protein thiol levels (PSH and NPSH), and O<sub>2</sub><sup>−</sup> production were assessed, alongside SOD1, GPx1, and GR gene expression. Results revealed a decrease in GPx, GR, and CAT activity after CuSO<sub>4</sub> exposure in both cell lines over 24-48 h, while SOD activity initially increased, then declined after 48 h. CK activity was also decreased in C6 cells. NPSH and PSH levels dropped after 24 h, and O<sub>2</sub><sup>−</sup> production was observed in all CuSO<sub>4</sub> concentrations. GR mRNA was reduced in both cell lines, contrasting with increased GPx1 mRNA in C6. U-87 MG cells exhibited higher levels of SOD1 mRNA, while C6 cells displayed lower expression. Our findings suggest that copper excess limits antioxidant enzyme activity and thiol levels, particularly in the C6 cells, likely attributable to oxidative stress or direct copper-enzyme interactions. Moreover, our results imply differences in copper toxicity regarding the cell lineage used, highlighting the importance of analyzing high copper levels effects in different models. Moreover, it could be proposed that the antioxidant system is a target of copper toxicity, contributing to glioma cell death.</div></div>","PeriodicalId":10602,"journal":{"name":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","volume":"287 ","pages":"Article 110065"},"PeriodicalIF":3.9000,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Comparative Biochemistry and Physiology C-toxicology & Pharmacology","FirstCategoryId":"93","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1532045624002333","RegionNum":3,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Copper excess has been tested as an anticancer therapy, due to its properties to generate oxidative stress resulting in tumoral cell death. Thus, this study aimed to evaluate the impact of copper excess on oxidative stress and antioxidant responses in glioma cells, establishing the antioxidant system as a target of copper toxicity in tumoral cells. C6 and U-87 MG cells were exposed to CuSO4 (0–600 μM) for 24-48 h. SOD, CAT, GPx, GR, and CK activities, protein and non-protein thiol levels (PSH and NPSH), and O2− production were assessed, alongside SOD1, GPx1, and GR gene expression. Results revealed a decrease in GPx, GR, and CAT activity after CuSO4 exposure in both cell lines over 24-48 h, while SOD activity initially increased, then declined after 48 h. CK activity was also decreased in C6 cells. NPSH and PSH levels dropped after 24 h, and O2− production was observed in all CuSO4 concentrations. GR mRNA was reduced in both cell lines, contrasting with increased GPx1 mRNA in C6. U-87 MG cells exhibited higher levels of SOD1 mRNA, while C6 cells displayed lower expression. Our findings suggest that copper excess limits antioxidant enzyme activity and thiol levels, particularly in the C6 cells, likely attributable to oxidative stress or direct copper-enzyme interactions. Moreover, our results imply differences in copper toxicity regarding the cell lineage used, highlighting the importance of analyzing high copper levels effects in different models. Moreover, it could be proposed that the antioxidant system is a target of copper toxicity, contributing to glioma cell death.
期刊介绍:
Part C: Toxicology and Pharmacology. This journal is concerned with chemical and drug action at different levels of organization, biotransformation of xenobiotics, mechanisms of toxicity, including reactive oxygen species and carcinogenesis, endocrine disruptors, natural products chemistry, and signal transduction with a molecular approach to these fields.