Epigenetic upregulation of galanin-like peptide mediates deoxynivalenol induced-growth inhibition in pituitary cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F20%3A50017125" target="_blank" >RIV/62690094:18470/20:50017125 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0041008X20302921" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0041008X20302921</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.taap.2020.115166" target="_blank" >10.1016/j.taap.2020.115166</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Epigenetic upregulation of galanin-like peptide mediates deoxynivalenol induced-growth inhibition in pituitary cells

Popis výsledku v původním jazyce

Deoxynivalenol (DON) is an unavoidable contaminant in human food, animal feeds, and agricultural products. Growth retardation in children caused by extensive DON pollution has become a global problem that cannot be ignored. Previous studies have shown that DON causes stunting in children through intestinal dysfunction, insulin-like growth factor-1 (IGF-1) axis disorder and peptide YY (PYY). Galanin-like peptide (GALP) is an important growth regulator, but its role in DON-induced growth retardation is unclear. In this study, we report the important role of GALP during DON-induced growth inhibition in the rat pituitary tumour cell line GH3. DON was found to increase the expression of GALP through hypomethylationin the promoter region of the GALP gene and upregulate the expression of proinflammatory factors, while downregulate the expression of growth hormone (GH). Furthermore, GALP overexpression promoted proinflammatory cytokines, including TNF-alpha, IL-1 beta, IL-11 and IL-6, and further reduced cell viability and cell proliferation, while the inhibitory effect of GALP was the opposite. The expression of GALP and insulin like growth factor binding protein acid labile subunit (IGFALS) showed the opposite trend, which was the potential reason for the regulation of cell proliferation by GALP. In addition, GALP has anti-apoptotic effects, which could not eliminate the inflammatory damage of cells, thus aggravating cell growth inhibition. The present findings provide new mechanistic insights into the toxicity of DON-induced growth retardation and suggest a therapeutic potential of GALP in DON-related diseases.

Název v anglickém jazyce

Epigenetic upregulation of galanin-like peptide mediates deoxynivalenol induced-growth inhibition in pituitary cells

Popis výsledku anglicky

Deoxynivalenol (DON) is an unavoidable contaminant in human food, animal feeds, and agricultural products. Growth retardation in children caused by extensive DON pollution has become a global problem that cannot be ignored. Previous studies have shown that DON causes stunting in children through intestinal dysfunction, insulin-like growth factor-1 (IGF-1) axis disorder and peptide YY (PYY). Galanin-like peptide (GALP) is an important growth regulator, but its role in DON-induced growth retardation is unclear. In this study, we report the important role of GALP during DON-induced growth inhibition in the rat pituitary tumour cell line GH3. DON was found to increase the expression of GALP through hypomethylationin the promoter region of the GALP gene and upregulate the expression of proinflammatory factors, while downregulate the expression of growth hormone (GH). Furthermore, GALP overexpression promoted proinflammatory cytokines, including TNF-alpha, IL-1 beta, IL-11 and IL-6, and further reduced cell viability and cell proliferation, while the inhibitory effect of GALP was the opposite. The expression of GALP and insulin like growth factor binding protein acid labile subunit (IGFALS) showed the opposite trend, which was the potential reason for the regulation of cell proliferation by GALP. In addition, GALP has anti-apoptotic effects, which could not eliminate the inflammatory damage of cells, thus aggravating cell growth inhibition. The present findings provide new mechanistic insights into the toxicity of DON-induced growth retardation and suggest a therapeutic potential of GALP in DON-related diseases.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

TOXICOLOGY AND APPLIED PHARMACOLOGY

ISSN

0041-008X

e-ISSN

—

Svazek periodika

403

Číslo periodika v rámci svazku

September

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

"Article Number: 115166"

Kód UT WoS článku

000566899200001

EID výsledku v databázi Scopus

2-s2.0-85088856325