Tumor-promoting cyanotoxin microcystin-LR does not induce
procarcinogenic events in adult human liver stem cells

J 2018

Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells

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

Základní údaje

Originální název

Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells

Autoři

RAŠKA, Jan; Lucie ČTVERÁČKOVÁ; Aneta DYDOWICZOVÁ; Iva SOVADINOVÁ ; Luděk BLÁHA a Pavel BABICA

Vydání

Toxicology and applied pharmacology, SAN DIEGO, ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018, 0041-008X

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30108 Toxicology

Stát vydavatele

Spojené státy

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 3.585

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14310/18:00100980

Organizační jednotka

Přírodovědecká fakulta

Klíčová slova anglicky

HL1-hT1; Microcystin-LR; Adult liver stem cells; Liver tumor-promotion; OATP; Multidrug resistance proteins

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 6. 2018 11:41, Mgr. Michaela Hylsová, Ph.D.

Anotace

V originále

HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, alpha-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed. Cellular accumulation of MC-LR occurred most likely via mechanisms independent on organic anion transporting polypeptides (OATPs) or multidrug resistance (MDR) proteins, as indicated (a) by a gene expression analysis of 11 human OATP genes and 4 major MDR genes (MDR1/P-gly-coprotein, MRP1, MRP2 and BCRP); (b) by non-significant effects of OATP or MDR1 inhibitors on MC-LR uptake. Accumulation of MC-positive protein bands in HL1-hT1 cells was associated neither with alterations of cell viability and growth, dysregulations of ERK1/2 and p38 kinases, reactive oxygen species formation, induction of double-stranded DNA breaks nor modulations of stress-inducible genes (ATF3, HSP5). It suggests that LSCs might have a selective, MDR1-independent, survival advantage and higher tolerance towards MC-induced cytotoxic, genotoxic or cancer-related events than differentiated adult hepatocytes, fetal hepatocyte or malignant liver cell lines. HL1-hT1 cells provide a valuable in vitro tool for studying effects of toxicants and pharmaceuticals on LSCs, whose important role in the development of chronic toxicities and liver diseases is being increasingly recognized.

Návaznosti

CZ.02.1.01/0.0/0.0/16_013/0001761, interní kód MU

Název: RECETOX RI - OP VVV (Akronym: RECETOX RI)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, RECETOX RI - OP VVV, PO 1 Posilování kapacit pro kvalitní výzkum

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. Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells. Toxicology and applied pharmacology. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018, roč. 345, April, s. 103-113. ISSN 0041-008X. Dostupné z: https://doi.org/10.1016/j.taap.2018.03.011.

@article{1419437,
   author = {Raška, Jan and Čtveráčková, Lucie and Dydowiczová, Aneta and Sovadinová, Iva and Bláha, Luděk and Babica, Pavel},
   article_location = {SAN DIEGO},
   article_number = {April},
   doi = {https://doi.org/10.1016/j.taap.2018.03.011},
   keywords = {HL1-hT1; Microcystin-LR; Adult liver stem cells; Liver tumor-promotion; OATP; Multidrug resistance proteins},
   language = {eng},
   issn = {0041-008X},
   journal = {Toxicology and applied pharmacology},
   title = {Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells},
   url = {https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub},
   volume = {345},
   year = {2018}
}

TY  - JOUR
ID  - 1419437
AU  - Raška, Jan - Čtveráčková, Lucie - Dydowiczová, Aneta - Sovadinová, Iva - Bláha, Luděk - Babica, Pavel
PY  - 2018
TI  - Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells
JF  - Toxicology and applied pharmacology
VL  - 345
IS  - April
SP  - 103-113
EP  - 103-113
PB  - ACADEMIC PRESS INC ELSEVIER SCIENCE
SN  - 0041008X
KW  - HL1-hT1
KW  - Microcystin-LR
KW  - Adult liver stem cells
KW  - Liver tumor-promotion
KW  - OATP
KW  - Multidrug resistance proteins
UR  - https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0041008X18300899?via%3Dihub
N2  - HL1-hT1 cell line represents adult human liver stem cells (LSCs) immortalized with human telomerase reverse transcriptase. In this study, HL1-hT1 cells were found to express mesenchymal markers (vimentin, CD73, CD90/THY-1 and CD105) and an early hepatic endoderm marker FOXA2, while not expressing hepatic progenitor (HNF4A, LGR5, alpha-fetoprotein) or differentiated hepatocyte markers (albumin, transthyretin, connexin 32). In response to microcystin-LR (MC-LR), a time- and concentration-dependent formation of MC-positive protein bands in HL1-hT1 cells was observed. Cellular accumulation of MC-LR occurred most likely via mechanisms independent on organic anion transporting polypeptides (OATPs) or multidrug resistance (MDR) proteins, as indicated (a) by a gene expression analysis of 11 human OATP genes and 4 major MDR genes (MDR1/P-gly-coprotein, MRP1, MRP2 and BCRP); (b) by non-significant effects of OATP or MDR1 inhibitors on MC-LR uptake. Accumulation of MC-positive protein bands in HL1-hT1 cells was associated neither with alterations of cell viability and growth, dysregulations of ERK1/2 and p38 kinases, reactive oxygen species formation, induction of double-stranded DNA breaks nor modulations of stress-inducible genes (ATF3, HSP5). It suggests that LSCs might have a selective, MDR1-independent, survival advantage and higher tolerance towards MC-induced cytotoxic, genotoxic or cancer-related events than differentiated adult hepatocytes, fetal hepatocyte or malignant liver cell lines. HL1-hT1 cells provide a valuable in vitro tool for studying effects of toxicants and pharmaceuticals on LSCs, whose important role in the development of chronic toxicities and liver diseases is being increasingly recognized.
ER  -

RAŠKA, Jan; Lucie ČTVERÁČKOVÁ; Aneta DYDOWICZOVÁ; Iva SOVADINOVÁ; Luděk BLÁHA a Pavel BABICA. Tumor-promoting cyanotoxin microcystin-LR does not induce procarcinogenic events in adult human liver stem cells. \textit{Toxicology and applied pharmacology}. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE, 2018, roč.~345, April, s.~103-113. ISSN~0041-008X. Dostupné z: https://doi.org/10.1016/j.taap.2018.03.011.

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