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The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells
N. Capková, V. Pospíšilová, V. Fedorová, J. Raška, K. Pospíšilová, M. Dal Ben, A. Dvořák, J. Viktorová, D. Bohačiaková, L. Vítek
Jazyk angličtina Země Švýcarsko
Typ dokumentu časopisecké články
Grantová podpora
RVO-VFN64165/2021
Ministerstvo Zdravotnictví Ceské Republiky
NV18-07-00342
Agentura Pro Zdravotnický Výzkum České Republiky
21-01799S
Grantová Agentura České Republiky
18-25429Y
Grantová Agentura České Republiky
INBIO (No. CZ.02.1.01/0.0/0.0/16_026/0008451)
European Regional Development Fund
National Program of Sustainability II Project no. LQ1605
Ministerstvo Školství, Mládeže a Tělovýchovy
NLK
Directory of Open Access Journals
od 2012
PubMed Central
od 2012
Europe PubMed Central
od 2012
ProQuest Central
od 2012-03-01
Open Access Digital Library
od 2012-01-01
Open Access Digital Library
od 2012-01-01
ROAD: Directory of Open Access Scholarly Resources
od 2012
PubMed
34679668
DOI
10.3390/antiox10101532
Knihovny.cz E-zdroje
- Publikační typ
- časopisecké články MeSH
The 'gold standard' treatment of severe neonatal jaundice is phototherapy with blue-green light, which produces more polar photo-oxidation products that are easily excreted via the bile or urine. The aim of this study was to compare the effects of bilirubin (BR) and its major photo-oxidation product lumirubin (LR) on the proliferation, differentiation, morphology, and specific gene and protein expressions of self-renewing human pluripotent stem cell-derived neural stem cells (NSC). Neither BR nor LR in biologically relevant concentrations (12.5 and 25 µmol/L) affected cell proliferation or the cell cycle phases of NSC. Although none of these pigments affected terminal differentiation to neurons and astrocytes, when compared to LR, BR exerted a dose-dependent cytotoxicity on self-renewing NSC. In contrast, LR had a substantial effect on the morphology of the NSC, inducing them to form highly polar rosette-like structures associated with the redistribution of specific cellular proteins (β-catenin/N-cadherin) responsible for membrane polarity. This observation was accompanied by lower expressions of NSC-specific proteins (such as SOX1, NR2F2, or PAX6) together with the upregulation of phospho-ERK. Collectively, the data indicated that both BR and LR affect early human neurodevelopment in vitro, which may have clinical relevance in phototherapy-treated hyperbilirubinemic neonates.
Citace poskytuje Crossref.org
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- $a The 'gold standard' treatment of severe neonatal jaundice is phototherapy with blue-green light, which produces more polar photo-oxidation products that are easily excreted via the bile or urine. The aim of this study was to compare the effects of bilirubin (BR) and its major photo-oxidation product lumirubin (LR) on the proliferation, differentiation, morphology, and specific gene and protein expressions of self-renewing human pluripotent stem cell-derived neural stem cells (NSC). Neither BR nor LR in biologically relevant concentrations (12.5 and 25 µmol/L) affected cell proliferation or the cell cycle phases of NSC. Although none of these pigments affected terminal differentiation to neurons and astrocytes, when compared to LR, BR exerted a dose-dependent cytotoxicity on self-renewing NSC. In contrast, LR had a substantial effect on the morphology of the NSC, inducing them to form highly polar rosette-like structures associated with the redistribution of specific cellular proteins (β-catenin/N-cadherin) responsible for membrane polarity. This observation was accompanied by lower expressions of NSC-specific proteins (such as SOX1, NR2F2, or PAX6) together with the upregulation of phospho-ERK. Collectively, the data indicated that both BR and LR affect early human neurodevelopment in vitro, which may have clinical relevance in phototherapy-treated hyperbilirubinemic neonates.
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