{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T09:30:35Z","timestamp":1768037435867,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,29]],"date-time":"2022-07-29T00:00:00Z","timestamp":1659052800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-FAR\/31136\/2017"],"award-info":[{"award-number":["PTDC\/MED-FAR\/31136\/2017"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["UID\/DTP\/04138\/2019"],"award-info":[{"award-number":["UID\/DTP\/04138\/2019"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","doi-asserted-by":"publisher","award":["DL57\/2016\/CP1376\/CT002"],"award-info":[{"award-number":["DL57\/2016\/CP1376\/CT002"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["(NIEHS) R01ES07331"],"award-info":[{"award-number":["(NIEHS) R01ES07331"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Mercury (Hg) is known for its neurotoxicity and is reported to activate microglia cells at low exposure levels. Since mercury decreases the activity of the glutathione and thioredoxin systems, we hypothesize that Hg would, in turn, disrupt microglia homeostasis by interfering with redox regulation of signaling pathways. Thus, in this work, we analyzed the effect of exposure to Hg2+ on nuclear translocation and activation of NF-kB (p50) and p38 and pro-inflammatory gene transcription (IL-1\u00df; iNOS, TNF-alpha) considering the interaction of Hg with the glutathione system and thioredoxin systems in microglial cells. N9 (mouse) microglia cells were exposed to different concentrations of Hg2+ and the 24 h EC50 for a reduction in viability was 42.1 \u00b1 3.7 \u03bcM. Subsequent experiments showed that at sub-cytotoxic levels of Hg2+, there was a general increase in ROS (\u224840%) accompanied by a significant depletion (60\u201390%) of glutathione (GSH) and thioredoxin reductase (TrxR) activity. Upon 6 h of exposure to Hg2+, p38 (but not p50) accumulated in the nucleus (50% higher than in control), which was accompanied by an increase in its phosphorylation. Transcript levels of both IL1-\u00df and iNOS were increased over two-fold relative to the control. Furthermore, pre-exposure of cells to the p38 inhibitor SB 239063 hindered the activation of cytokine transcription by Hg2+. These results show that disruption of redox systems by Hg2+ prompts the activation of p38 leading to transcription of pro-inflammatory genes in microglia cells. Treatment of N9 cells with NAC or sodium selenite\u2014which caused an increase in basal GSH and TrxR levels, respectively, prevented the activation of p38 and the transcription of pro-inflammatory cytokines. This result demonstrates the importance of an adequate nutritional status to minimize the toxicity resulting from Hg exposure in human populations at risk.<\/jats:p>","DOI":"10.3390\/toxics10080433","type":"journal-article","created":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T23:49:27Z","timestamp":1659397767000},"page":"433","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["N-Acetylcysteine or Sodium Selenite Prevent the p38-Mediated Production of Proinflammatory Cytokines by Microglia during Exposure to Mercury (II)"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0466-4934","authenticated-orcid":false,"given":"Vasco","family":"Branco","sequence":"first","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"},{"name":"Centro de Investiga\u00e7\u00e3o Interdisciplinar Egas Moniz (CiiEM), Instituto Universit\u00e1rio Egas Moniz (IUEM), 2829-511 Caparica, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6902-6346","authenticated-orcid":false,"given":"Lucia","family":"Coppo","sequence":"additional","affiliation":[{"name":"Division of Biochemistry, Department of Medical Biochemistry and Biophysics, Karolinska Institute, SE-171 77 Stockholm, Sweden"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2619-1656","authenticated-orcid":false,"given":"Michael","family":"Aschner","sequence":"additional","affiliation":[{"name":"Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA"}]},{"given":"Cristina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, 1649-003 Lisbon, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"609","DOI":"10.1080\/10408440600845619","article-title":"The toxicology of mercury and its chemical compounds","volume":"36","author":"Clarkson","year":"2006","journal-title":"Crit. 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