{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:22:42Z","timestamp":1760235762115,"version":"build-2065373602"},"reference-count":56,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2021,9,22]],"date-time":"2021-09-22T00:00:00Z","timestamp":1632268800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"Narodowe Centrum Nauki","doi-asserted-by":"publisher","award":["2017\/25\/B\/NZ5\/01961"],"award-info":[{"award-number":["2017\/25\/B\/NZ5\/01961"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Preeclampsia is a pregnancy disorder associated with shallow placentation, forcing placental cells to live in hypoxic conditions. This activates the transcription factor kappa B (NF\u03baB) in maternal and placental cells. Although the role of NF\u03baB in preeclampsia is well documented, its mechanism of activation in trophoblastic cells has been never studied. This study investigates the mechanism of NF\u03baB activation in a first trimester trophoblastic cell line (HTR8\/SVneo) stimulated by a medium containing serum from preeclamptic (PE) or normotensive (C) women in hypoxic (2% O2) or normoxic (8% O2) conditions. The results indicate that in HTR8\/SVneo cells, the most widely studied NF\u03baB pathways, i.e., canonical, non-canonical and atypical, are downregulated in environment PE 2% O2 in comparison to C 8% O2. Therefore, other pathways may be responsible for NF\u03baB activation. One such pathway depends on the activation of NF\u03baB by the p53\/RSK1 complex through its phosphorylation at Serine 536 (pNF\u03baB Ser536). The data generated by our study show that inhibition of the p53\/RSK1 pathway by p53-targeted siRNA results in a depletion of pNF\u03baB Ser536 in the nucleus, but only in cells incubated with PE serum at 2% O2. Thus, the p53\/RSK1 complex might play a critical role in the activation of NF\u03baB in trophoblastic cells and preeclamptic placentas.<\/jats:p>","DOI":"10.3390\/ijms221910200","type":"journal-article","created":{"date-parts":[[2021,9,24]],"date-time":"2021-09-24T20:15:32Z","timestamp":1632514532000},"page":"10200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Preeclamptic Environment Promotes the Activation of Transcription Factor Kappa B by P53\/RSK1 Complex in a HTR8\/SVneo Trophoblastic Cell Line"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5083-2046","authenticated-orcid":false,"given":"Agata","family":"Sakowicz","sequence":"first","affiliation":[{"name":"Department of Medical Biotechnology, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6127-4481","authenticated-orcid":false,"given":"Michalina","family":"Bralewska","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tadeusz","family":"Pietrucha","sequence":"additional","affiliation":[{"name":"Department of Medical Biotechnology, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesc","family":"Figueras","sequence":"additional","affiliation":[{"name":"Barcelona Center of Maternal-Fetal Medicine and Neonatology (Hospital Clinic and Hospital Sant Joan de Deu), IDIBAPS, University of Barcelona, 08036 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0699-7441","authenticated-orcid":false,"given":"Dominika E.","family":"Habrowska-G\u00f3rczy\u0144ska","sequence":"additional","affiliation":[{"name":"Department of Cell Culture and Genomic Analysis, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7462-8528","authenticated-orcid":false,"given":"Agnieszka W.","family":"Piastowska-Ciesielska","sequence":"additional","affiliation":[{"name":"Department of Cell Culture and Genomic Analysis, Medical University of Lodz, 90-752 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnieszka","family":"Gach","sequence":"additional","affiliation":[{"name":"Department of Genetics, Polish Mother\u2019s Memorial Hospital-Research Institute in Lodz, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5153-2398","authenticated-orcid":false,"given":"Bartosz","family":"Sakowicz","sequence":"additional","affiliation":[{"name":"Department of Microelectronics and Computer Science, Lodz University of Technology, 93-005 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6993-8078","authenticated-orcid":false,"given":"Magda","family":"Rybak-Krzyszkowska","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Perinatology, University Hospital in Krakow, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Huras","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Perinatology, University Hospital in Krakow, 31-501 Krakow, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6900-4347","authenticated-orcid":false,"given":"Mariusz","family":"Grzesiak","sequence":"additional","affiliation":[{"name":"Department of Perinatology, Obstetrics and Gynecology, Polish Mother\u2019s Memorial Hospital-Research Institute in Lodz, 93-338 Lodz, Poland"},{"name":"Department of Obstetrics and Gynecology, Medical University of Lodz, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lidia","family":"Biesiada","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Polish Mother\u2019s Memorial Hospital-Research Institute, 93-338 Lodz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,22]]},"reference":[{"key":"ref_1","first-page":"e137","article-title":"Regulation of trophoblast invasion: The role of matrix metalloproteinases","volume":"5","author":"Zhu","year":"2012","journal-title":"Rev. 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