{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T08:54:02Z","timestamp":1778316842187,"version":"3.51.4"},"reference-count":82,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Romanian Ministry of Education and Research, UEFISCDI","award":["PCE 39\/2022"],"award-info":[{"award-number":["PCE 39\/2022"]}]},{"name":"Romanian Ministry of Education and Research, UEFISCDI","award":["PN 23210202\/2023"],"award-info":[{"award-number":["PN 23210202\/2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Methylglyoxal is a reactive dicarbonyl intermediate in the advanced glycation end-product (AGE) pathway, and alterations in its levels have been detected in the plasma, cerebrospinal fluid, and brain parenchyma in various pathologies, particularly in diabetes. In this study, we investigate the effects of methylglyoxal (MGO) on murine brain microvascular endothelial cells at both physiological and pathological concentrations. We evaluate molecular parameters, including reactive oxygen species (ROS) production, cytosolic calcium signaling, and ATP synthesis, as well as cellular responses such as cytoskeletal remodeling, cell migration, adhesion, and permeability, across a concentration range of 0\u20131000 \u03bcM. At low concentrations (below ~250 \u03bcM), MGO does not induce oxidative stress; instead, it leads to an increase in cytosolic calcium levels and ATP production. At higher concentrations, however, MGO induces significant oxidative stress, which is accompanied by a marked decrease in cell viability, particularly at concentrations exceeding 500 \u03bcM. The modulation of key functional processes, including purinergic calcium signaling, actin filament synthesis, cell migration, and adhesion, reveals a threshold concentration beyond which cellular function is impaired due to oxidative stress. Below this threshold, the observed effects appear to be mediated primarily by non-oxidative mechanisms, likely involving protein glycation. In conclusion, our results suggest a dual action of methylglyoxal on brain endothelial cells, with distinct molecular mechanisms underlying its effects at physiological versus pathological concentrations.<\/jats:p>","DOI":"10.3390\/ijms26115104","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T11:12:57Z","timestamp":1748344377000},"page":"5104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Are You a Friend or an Enemy? The Dual Action of Methylglyoxal on Brain Microvascular Endothelial Cells"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0521-8645","authenticated-orcid":false,"given":"Roberta","family":"Mois\u0103 (Stoica)","sequence":"first","affiliation":[{"name":"Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"},{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, 077125 M\u0103gurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C\u0103lin Mircea","family":"Rusu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia Teona","family":"Deftu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7309-6002","authenticated-orcid":false,"given":"Mihaela","family":"Bacalum","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, 077125 M\u0103gurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1128-8153","authenticated-orcid":false,"given":"Mihai","family":"Radu","sequence":"additional","affiliation":[{"name":"Department of Life and Environmental Physics, Horia Hulubei National Institute for Physics and Nuclear Engineering, 077125 M\u0103gurele, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4421-2163","authenticated-orcid":false,"given":"Beatrice Mihaela","family":"Radu","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Animal Physiology and Biophysics, Faculty of Biology, University of Bucharest, 050095 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1016\/j.febslet.2006.01.086","article-title":"Heat-shock Protein 27 Is a Major Methylglyoxal-modified Protein in Endothelial Cells","volume":"580","author":"Schalkwijk","year":"2006","journal-title":"FEBS Lett."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Cai, M., Wang, H., Song, H., Yang, R., Wang, L., Xue, X., Sun, W., and Hu, J. 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