Katarina Živančević, Başak Aru, Abdullah Demir, Lidija Radenović, Pavle Andjus, Gülderen Yanıkkaya Demirel
{"title":"锌诱导的小胶质细胞细胞毒性和线粒体应激：免疫球蛋白 G 体外保护作用的意义","authors":"Katarina Živančević, Başak Aru, Abdullah Demir, Lidija Radenović, Pavle Andjus, Gülderen Yanıkkaya Demirel","doi":"10.4274/balkanmedj.galenos.2024.2024-4-119","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders.</p><p><strong>Aims: </strong>To investigate whether IgG treatment can alleviate oxidative stress caused by Zn<sup>0</sup> on microglia in vitro.</p><p><strong>Study design: </strong>In vitro study.</p><p><strong>Methods: </strong>The feasibility of Zn<sup>0</sup> treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn<sup>0</sup>, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B.</p><p><strong>Methods: </strong>The feasibility of Zn<sup>0</sup> treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn<sup>0</sup>, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn<sup>0</sup> cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn<sup>0</sup> neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn<sup>0</sup>-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn<sup>0</sup>-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn<sup>0</sup> exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn<sup>0</sup> decreased TRIM21 levels, which is reversed by IgG administration.</p><p><strong>Conclusion: </strong>These findings elucidate the cellular responses to Zn<sup>0</sup> and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn<sup>0</sup> exposure.</p>","PeriodicalId":8690,"journal":{"name":"Balkan Medical Journal","volume":" ","pages":"348-356"},"PeriodicalIF":1.9000,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Zn<sup>0</sup>-Induced Cytotoxicity and Mitochondrial Stress in Microglia: Implications of the Protective Role of Immunoglobulin G In Vitro\",\"authors\":\"Katarina Živančević, Başak Aru, Abdullah Demir, Lidija Radenović, Pavle Andjus, Gülderen Yanıkkaya Demirel\",\"doi\":\"10.4274/balkanmedj.galenos.2024.2024-4-119\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders.</p><p><strong>Aims: </strong>To investigate whether IgG treatment can alleviate oxidative stress caused by Zn<sup>0</sup> on microglia in vitro.</p><p><strong>Study design: </strong>In vitro study.</p><p><strong>Methods: </strong>The feasibility of Zn<sup>0</sup> treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn<sup>0</sup>, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B.</p><p><strong>Methods: </strong>The feasibility of Zn<sup>0</sup> treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn<sup>0</sup>, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn<sup>0</sup> cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn<sup>0</sup> neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn<sup>0</sup>-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn<sup>0</sup>-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn<sup>0</sup> exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn<sup>0</sup> decreased TRIM21 levels, which is reversed by IgG administration.</p><p><strong>Conclusion: </strong>These findings elucidate the cellular responses to Zn<sup>0</sup> and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn<sup>0</sup> exposure.</p>\",\"PeriodicalId\":8690,\"journal\":{\"name\":\"Balkan Medical Journal\",\"volume\":\" \",\"pages\":\"348-356\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2024-09-06\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Balkan Medical Journal\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.4274/balkanmedj.galenos.2024.2024-4-119\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/8/12 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q2\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Balkan Medical Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.4274/balkanmedj.galenos.2024.2024-4-119","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/12 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Zn0-Induced Cytotoxicity and Mitochondrial Stress in Microglia: Implications of the Protective Role of Immunoglobulin G In Vitro
Background: Zinc (Zn), an essential micronutrient, regulates and maintains neurological functions. However, both Zn deficiency and excess can cause oxidative stress and neurodegenerative diseases. As previously reported, immunoglobulin G (IgG) can modulate oxidative stress in various disorders.
Aims: To investigate whether IgG treatment can alleviate oxidative stress caused by Zn0 on microglia in vitro.
Study design: In vitro study.
Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B.
Methods: The feasibility of Zn0 treatment was evaluated using the MTS assay. Oxidative stress following treatment with Zn0, either alone or with IgG supplementation, was determined with dihydrorhodamine 123 staining. Flow cytometry was employed to ascertain the intracellular protein levels of TRIM21, PINK, PARKIN, MFN2, Beclin-1, and active LC3B. Results: In silico screening confirmed the association between Zn0 cytotoxicity and apoptosis. Furthermore, oxidative stress was identified as a critical mechanism that underlies Zn0 neurotoxicity. The in silico analysis revealed that Zn can interact with the constant region of the Ig heavy chain, suggesting a potential role for IgG in alleviating Zn0-induced cytotoxicity. Experimental findings supported this hypothesis, as IgG administration significantly reduced Zn0-induced mitochondrial stress in a dose-dependent manner. The upregulation of PINK1 levels by Zn0 exposure suggests that mitochondrial injury promotes mitophagy. Interestingly, Zn0 decreased TRIM21 levels, which is reversed by IgG administration.
Conclusion: These findings elucidate the cellular responses to Zn0 and highlight the potential use of intravenous immunoglobulin in mitigating the adverse effects of acute Zn0 exposure.
期刊介绍：
The Balkan Medical Journal (Balkan Med J) is a peer-reviewed open-access international journal that publishes interesting clinical and experimental research conducted in all fields of medicine, interesting case reports and clinical images, invited reviews, editorials, letters, comments and letters to the Editor including reports on publication and research ethics. The journal is the official scientific publication of the Trakya University Faculty of Medicine, Edirne, Turkey and is printed six times a year, in January, March, May, July, September and November. The language of the journal is English.
The journal is based on independent and unbiased double-blinded peer-reviewed principles. Only unpublished papers that are not under review for publication elsewhere can be submitted. Balkan Medical Journal does not accept multiple submission and duplicate submission even though the previous one was published in a different language. The authors are responsible for the scientific content of the material to be published. The Balkan Medical Journal reserves the right to request any research materials on which the paper is based.
The Balkan Medical Journal encourages and enables academicians, researchers, specialists and primary care physicians of Balkan countries to publish their valuable research in all branches of medicine. The primary aim of the journal is to publish original articles with high scientific and ethical quality and serve as a good example of medical publications in the Balkans as well as in the World.
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