Cylindrospermopsin induces cellular stress and activation of
ERK1/2 and p38 MAPK pathways in adult human liver stem cells

J 2019

Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells

RAŠKA, Jan, Lucie ČTVERÁČKOVÁ, Aneta DYDOWICZOVÁ, Iva SOVADINOVÁ, Luděk BLÁHA et. al.

Základní údaje

Originální název

Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells

Autoři

RAŠKA, Jan (203 Česká republika, domácí), Lucie ČTVERÁČKOVÁ (203 Česká republika, domácí), Aneta DYDOWICZOVÁ (203 Česká republika, domácí), Iva SOVADINOVÁ (203 Česká republika, domácí), Luděk BLÁHA (203 Česká republika, domácí) a Pavel BABICA (203 Česká republika, garant, domácí)

Vydání

Chemosphere, Oxford, PERGAMON-ELSEVIER SCIENCE LTD, 2019, 0045-6535

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10511 Environmental sciences

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

Full Text

Impakt faktor

Impact factor: 5.778

Kód RIV

RIV/00216224:14310/19:00107574

Organizační jednotka

Přírodovědecká fakulta

DOI

http://dx.doi.org/10.1016/j.chemosphere.2019.03.131

UT WoS

000469903400006

Klíčová slova anglicky

Adult human liver stem cells HL1-hT1; Cylindrospermopsin; DNA damage; Mitogen-activated protein kinases; Nongenotoxic mechanisms; Oxidative stress

Štítky

rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 24. 3. 2020 12:50, Mgr. Marie Šípková, DiS.

Anotace

V originále

Cyanobacterial toxin cylindrospermopsin (CYN) is an emerging freshwater contaminant, whose expanding environmental occurrence might result into increased human health risks. CYN is potent hepatotoxin, with cytotoxicity and genotoxicity documented in primary hepatocytes or hepatoma cell lines. However, there is only limited information about CYN effects on adult human liver stem cells (LSCs), which play an important role in liver tissue development, regeneration and repair. In our study with human liver cell line HL1-hT1 which expresses characteristics of LSC5, CYN was found to be cytotoxic and increasing cell death after 24-48 h exposure to concentrations >1 mu M. Subcytotoxic 1 mu M concentration did not induce cell death or membrane damage, but inhibited cellular processes related to energy production, leading to a growth stagnation after >72 h. Interestingly, these effects were not associated with increased DNA damage, reactive oxygen species production, or endoplasmic reticulum stress. However, CYN induced a sustained (24-48 h) activation of mitogen-activated protein kinases ERK1/2 and p38, and increased expression of stress-related transcription factor ATF3. Thus, LSC5 were not primarily affected by CYN-induced genotoxicity and oxidative stress, but via activation of signaling and transcriptional pathways critical for regulation of cell proliferation, stress responses, cell survival and inflammation. Alterations of LSCs during CYN-induced liver injury, including the role of nongenotoxic mechanisms, should be therefore considered in mechanistic assessments of chronic CYN hepatotoxicity and hepatocarcinogenicity.

Návaznosti

EF16_013/0001761, projekt VaV

Název: RECETOX RI

GA15-12408S, projekt VaV

Název: Role kmenových a diferencovaných jaterních buněk v hepatotoxicitě a hepatokarcinogenitě indukované cyanotoxiny

Investor: Grantová agentura ČR, Role kmenových a diferencovaných jaterních buněk v hepatotoxicitě a hepatokarcinogenitě indukované cyanotoxiny

LM2015051, projekt VaV

Název: Centrum pro výzkum toxických látek v prostředí (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Výzkumná infrastruktura RECETOX

Citovat

RAŠKA, Jan, Lucie ČTVERÁČKOVÁ, Aneta DYDOWICZOVÁ, Iva SOVADINOVÁ, Luděk BLÁHA a Pavel BABICA. Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells. Chemosphere. Oxford: PERGAMON-ELSEVIER SCIENCE LTD, 2019, roč. 227, July, s. 43-52. ISSN 0045-6535. Dostupné z: https://dx.doi.org/10.1016/j.chemosphere.2019.03.131.

@article{1549504,
   author = {Raška, Jan and Čtveráčková, Lucie and Dydowiczová, Aneta and Sovadinová, Iva and Bláha, Luděk and Babica, Pavel},
   article_location = {Oxford},
   article_number = {July},
   doi = {http://dx.doi.org/10.1016/j.chemosphere.2019.03.131},
   keywords = {Adult human liver stem cells HL1-hT1; Cylindrospermopsin; DNA damage; Mitogen-activated protein kinases; Nongenotoxic mechanisms; Oxidative stress},
   language = {eng},
   issn = {0045-6535},
   journal = {Chemosphere},
   title = {Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells},
   url = {https://www.sciencedirect.com/science/article/pii/S0045653519305739?via%3Dihub},
   volume = {227},
   year = {2019}
}

TY  - JOUR
ID  - 1549504
AU  - Raška, Jan - Čtveráčková, Lucie - Dydowiczová, Aneta - Sovadinová, Iva - Bláha, Luděk - Babica, Pavel
PY  - 2019
TI  - Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells
JF  - Chemosphere
VL  - 227
IS  - July
SP  - 43-52
EP  - 43-52
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 00456535
KW  - Adult human liver stem cells HL1-hT1
KW  - Cylindrospermopsin
KW  - DNA damage
KW  - Mitogen-activated protein kinases
KW  - Nongenotoxic mechanisms
KW  - Oxidative stress
UR  - https://www.sciencedirect.com/science/article/pii/S0045653519305739?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0045653519305739?via%3Dihub
N2  - Cyanobacterial toxin cylindrospermopsin (CYN) is an emerging freshwater contaminant, whose expanding environmental occurrence might result into increased human health risks. CYN is potent hepatotoxin, with cytotoxicity and genotoxicity documented in primary hepatocytes or hepatoma cell lines. However, there is only limited information about CYN effects on adult human liver stem cells (LSCs), which play an important role in liver tissue development, regeneration and repair. In our study with human liver cell line HL1-hT1 which expresses characteristics of LSC5, CYN was found to be cytotoxic and increasing cell death after 24-48 h exposure to concentrations >1 mu M. Subcytotoxic 1 mu M concentration did not induce cell death or membrane damage, but inhibited cellular processes related to energy production, leading to a growth stagnation after >72 h. Interestingly, these effects were not associated with increased DNA damage, reactive oxygen species production, or endoplasmic reticulum stress. However, CYN induced a sustained (24-48 h) activation of mitogen-activated protein kinases ERK1/2 and p38, and increased expression of stress-related transcription factor ATF3. Thus, LSC5 were not primarily affected by CYN-induced genotoxicity and oxidative stress, but via activation of signaling and transcriptional pathways critical for regulation of cell proliferation, stress responses, cell survival and inflammation. Alterations of LSCs during CYN-induced liver injury, including the role of nongenotoxic mechanisms, should be therefore considered in mechanistic assessments of chronic CYN hepatotoxicity and hepatocarcinogenicity.
ER  -

RAŠKA, Jan, Lucie ČTVERÁČKOVÁ, Aneta DYDOWICZOVÁ, Iva SOVADINOVÁ, Luděk BLÁHA a Pavel BABICA. Cylindrospermopsin induces cellular stress and activation of ERK1/2 and p38 MAPK pathways in adult human liver stem cells. \textit{Chemosphere}. Oxford: PERGAMON-ELSEVIER SCIENCE LTD, 2019, roč.~227, July, s.~43-52. ISSN~0045-6535. Dostupné z: https://dx.doi.org/10.1016/j.chemosphere.2019.03.131.

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