The Effects of Bilirubin and Lumirubin on the Differentiation
of Human Pluripotent Cell-Derived Neural Stem Cells

J 2021

The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells

CAPKOVA, Nikola, Veronika POSPÍŠILOVÁ, Veronika FEDOROVÁ, Jan RAŠKA, Katerina POSPISILOVA et. al.

Basic information

Original name

The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells

Authors

CAPKOVA, Nikola (203 Czech Republic), Veronika POSPÍŠILOVÁ (203 Czech Republic, belonging to the institution), Veronika FEDOROVÁ (203 Czech Republic, belonging to the institution), Jan RAŠKA (203 Czech Republic, belonging to the institution), Katerina POSPISILOVA (203 Czech Republic), Matteo DAL BEN, Ales DVORAK (203 Czech Republic), Jitka VIKTOROVA (203 Czech Republic), Dáša BOHAČIAKOVÁ (703 Slovakia, belonging to the institution) and Libor VITEK (203 Czech Republic, guarantor)

Edition

Antioxidants, Basel, MDPI, 2021, 2076-3921

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10608 Biochemistry and molecular biology

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 7.675

RIV identification code

RIV/00216224:14110/21:00119650

Organization unit

Faculty of Medicine

DOI

http://dx.doi.org/10.3390/antiox10101532

UT WoS

000712298000001

Keywords in English

bilirubin; neurodevelopment; phototherapy

Abstract

V originále

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 mu mol/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 (beta-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.

Links

GA21-01799S, research and development project

Name: Flavonoidy jako unikátní třída molekul fotochemicky uvolňujících oxid uhelnatý

Investor: Czech Science Foundation

GJ18-25429Y, research and development project

Name: Funkční studie mikroRNA u nerálních kmenových buněk v průběhu diferenciace

Investor: Czech Science Foundation

LM2018129, research and development project

Name: Národní infrastruktura pro biologické a medicínské zobrazování Czech-BioImaging

Investor: Ministry of Education, Youth and Sports of the CR

NV18-07-00342, research and development project

Name: Studium degradačních produktů bilirubinu vznikajících při fototerapii novorozenecké žloutenky

Investor: Ministry of Health of the CR

Citovat

CAPKOVA, Nikola, Veronika POSPÍŠILOVÁ, Veronika FEDOROVÁ, Jan RAŠKA, Katerina POSPISILOVA, Matteo DAL BEN, Ales DVORAK, Jitka VIKTOROVA, Dáša BOHAČIAKOVÁ and Libor VITEK. The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells. Antioxidants. Basel: MDPI, 2021, vol. 10, No 10, p. 1-16. ISSN 2076-3921. Available from: https://dx.doi.org/10.3390/antiox10101532.

@article{1834647,
   author = {Capkova, Nikola and Pospíšilová, Veronika and Fedorová, Veronika and Raška, Jan and Pospisilova, Katerina and Dal Ben, Matteo and Dvorak, Ales and Viktorova, Jitka and Bohačiaková, Dáša and Vitek, Libor},
   article_location = {Basel},
   article_number = {10},
   doi = {http://dx.doi.org/10.3390/antiox10101532},
   keywords = {bilirubin; neurodevelopment; phototherapy},
   language = {eng},
   issn = {2076-3921},
   journal = {Antioxidants},
   title = {The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells},
   url = {https://www.mdpi.com/2076-3921/10/10/1532},
   volume = {10},
   year = {2021}
}

TY  - JOUR
ID  - 1834647
AU  - Capkova, Nikola - Pospíšilová, Veronika - Fedorová, Veronika - Raška, Jan - Pospisilova, Katerina - Dal Ben, Matteo - Dvorak, Ales - Viktorova, Jitka - Bohačiaková, Dáša - Vitek, Libor
PY  - 2021
TI  - The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells
JF  - Antioxidants
VL  - 10
IS  - 10
SP  - 1-16
EP  - 1-16
PB  - MDPI
SN  - 20763921
KW  - bilirubin
KW  - neurodevelopment
KW  - phototherapy
UR  - https://www.mdpi.com/2076-3921/10/10/1532
N2  - 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 mu mol/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 (beta-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.
ER  -

CAPKOVA, Nikola, Veronika POSPÍŠILOVÁ, Veronika FEDOROVÁ, Jan RAŠKA, Katerina POSPISILOVA, Matteo DAL BEN, Ales DVORAK, Jitka VIKTOROVA, Dáša BOHAČIAKOVÁ and Libor VITEK. The Effects of Bilirubin and Lumirubin on the Differentiation of Human Pluripotent Cell-Derived Neural Stem Cells. \textit{Antioxidants}. Basel: MDPI, 2021, vol.~10, No~10, p.~1-16. ISSN~2076-3921. Available from: https://dx.doi.org/10.3390/antiox10101532.

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