{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T22:04:54Z","timestamp":1768341894214,"version":"3.49.0"},"reference-count":43,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,24]],"date-time":"2019-11-24T00:00:00Z","timestamp":1574553600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004442","name":"National Science Centre","doi-asserted-by":"publisher","award":["PRELUDIUM 13, project 2017\/25\/N\/NZ7\/00978"],"award-info":[{"award-number":["PRELUDIUM 13, project 2017\/25\/N\/NZ7\/00978"]}],"id":[{"id":"10.13039\/501100004442","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Medical University of Silesia in Katowice","award":["KNW-1-037\/K\/9\/O, KNW-2-O41\/D\/9\/N, KNW-2-O31\/D\/8\/N"],"award-info":[{"award-number":["KNW-1-037\/K\/9\/O, KNW-2-O41\/D\/9\/N, KNW-2-O31\/D\/8\/N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Cobalamin deficiency is an important health problem. The major non-hematological symptoms of hypocobalaminemia are nervous system disorders, but the molecular and cellular mechanisms underlying this phenomenon have not yet been fully explained. Increasing scientific evidence is stressing the pivotal role of astrocyte dysfunction in the pathogenesis of a wide range of neurological disorders. In light of the above, the aim of this study was to develop an in vitro model of cobalamin deficiency by optimizing the conditions of astrocyte culture in the presence of vitamin B12 antagonist, and then the model was used for multidirectional analysis of astrocyte homeostasis using image cytometry, immunoenzymatic and colorimetric assays, and fluorescence spectroscopy. Our results indicated that long-term incubation of normal human astrocytes with hydroxycobalamin(c-lactam) causes an increase of extracellular homocysteine level, a reduction of cell proliferation, and an accumulation of cells in the G2\/M cell cycle phase. Moreover, we observed dramatic activation of caspases and an increase of catalase activity. Interestingly, we excluded extensive apoptosis and oxidative stress. The study provided significant evidence for astrocyte homeostasis disturbance under hypocobalaminemia, thus indicating an important element of the molecular mechanism of nervous system diseases related to vitamin B12 deficiency.<\/jats:p>","DOI":"10.3390\/cells8121505","type":"journal-article","created":{"date-parts":[[2019,11,25]],"date-time":"2019-11-25T03:10:00Z","timestamp":1574651400000},"page":"1505","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Cobalamin Deficiency: Effect on Homeostasis of Cultured Human Astrocytes"],"prefix":"10.3390","volume":"8","author":[{"given":"Zuzanna","family":"Rzepka","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jakub","family":"Rok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michalina","family":"Respondek","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Justyna","family":"Pawlik","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-3004","authenticated-orcid":false,"given":"Artur","family":"Beberok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5197-4222","authenticated-orcid":false,"given":"Dorota","family":"Gryko","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, Polish Academy of Science, Kasprzaka 44\/52, 01-224 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6918-3330","authenticated-orcid":false,"given":"Dorota","family":"Wrze\u015bniok","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Katowice, Poland, Jagiello\u0144ska 4, 41-200 Sosnowiec, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. 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