Molecular Characterization of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1 alpha (PGC1 alpha) and Its Role in Mitochondrial Biogenesis in Blunt Snout Bream (Megalobrama amblycephala)

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60076658%3A12520%2F19%3A43899078" target="_blank" >RIV/60076658:12520/19:43899078 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.frontiersin.org/articles/10.3389/fphys.2018.01957/full" target="_blank" >https://www.frontiersin.org/articles/10.3389/fphys.2018.01957/full</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3389/fphys.2018.01957" target="_blank" >10.3389/fphys.2018.01957</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Molecular Characterization of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1 alpha (PGC1 alpha) and Its Role in Mitochondrial Biogenesis in Blunt Snout Bream (Megalobrama amblycephala)

Popis výsledku v původním jazyce

PGC1 alpha is a transcriptional coactivator that plays key roles in mitochondrial biogenesis, so exploring its molecular characterization contributes to the understanding of mitochondrial function in cultured fish. In the present study, a full-length cDNA coding PGC1 alpha was cloned from the liver of blunt snout bream (Megalobrama amblycephala) which covered 3741 bp with an open reading frame of 2646 bp encoding 881 amino acids. Sequence alignment and phylogenetic analysis revealed high conservation with other fish species, as well as other higher vertebrates. Comparison of the derived amino acid sequences indicates that, as with other fish, there is a proline at position 176 (RIRP) compared to a Thr in the mammalian sequences (RIRT). To investigate PGC1 alpha function, three in vitro tests were carried out using primary hepatocytes of blunt snout bream. The effect of AMPK activity on the expression of PGC1 alpha was determined by the culture of the hepatocytes with an activator (Metformin) or inhibitor (Compound C) of AMPK. Neither AMPK activation nor inhibition altered PGC1 alpha expression. Knockdown of PGC1 alpha expression in hepatocytes using small interfering RNA (si-RNA) was used to determine the role of PGC1 alpha in mitochondrial biogenesis. No significant differences in the expression of NRF1 and TFAM, and mtDNA copy number were found between control and si-RNA groups. Also, hepatocytes were cultured with oleic acid, and the findings showed the significant reduction of mtDNA copy number in oleic acid group compared to control. Moreover, oleic acid down-regulated the expression of NRF1 and TFAM genes, while PGC1 alpha expression remained unchanged. Our findings support the proposal that PGC1 alpha may not play a role in mitochondrial biogenesis in blunt snout bream hepatocytes.

Název v anglickém jazyce

Molecular Characterization of Peroxisome Proliferator-Activated Receptor-Gamma Coactivator-1 alpha (PGC1 alpha) and Its Role in Mitochondrial Biogenesis in Blunt Snout Bream (Megalobrama amblycephala)

Popis výsledku anglicky

PGC1 alpha is a transcriptional coactivator that plays key roles in mitochondrial biogenesis, so exploring its molecular characterization contributes to the understanding of mitochondrial function in cultured fish. In the present study, a full-length cDNA coding PGC1 alpha was cloned from the liver of blunt snout bream (Megalobrama amblycephala) which covered 3741 bp with an open reading frame of 2646 bp encoding 881 amino acids. Sequence alignment and phylogenetic analysis revealed high conservation with other fish species, as well as other higher vertebrates. Comparison of the derived amino acid sequences indicates that, as with other fish, there is a proline at position 176 (RIRP) compared to a Thr in the mammalian sequences (RIRT). To investigate PGC1 alpha function, three in vitro tests were carried out using primary hepatocytes of blunt snout bream. The effect of AMPK activity on the expression of PGC1 alpha was determined by the culture of the hepatocytes with an activator (Metformin) or inhibitor (Compound C) of AMPK. Neither AMPK activation nor inhibition altered PGC1 alpha expression. Knockdown of PGC1 alpha expression in hepatocytes using small interfering RNA (si-RNA) was used to determine the role of PGC1 alpha in mitochondrial biogenesis. No significant differences in the expression of NRF1 and TFAM, and mtDNA copy number were found between control and si-RNA groups. Also, hepatocytes were cultured with oleic acid, and the findings showed the significant reduction of mtDNA copy number in oleic acid group compared to control. Moreover, oleic acid down-regulated the expression of NRF1 and TFAM genes, while PGC1 alpha expression remained unchanged. Our findings support the proposal that PGC1 alpha may not play a role in mitochondrial biogenesis in blunt snout bream hepatocytes.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Frontiers in Physiology

ISSN

1664-042X

e-ISSN

—

Svazek periodika

9

Číslo periodika v rámci svazku

neuveden

Stát vydavatele periodika

CH - Švýcarská konfederace

Počet stran výsledku

12

Strana od-do

—

Kód UT WoS článku

000456746800001

EID výsledku v databázi Scopus

2-s2.0-85065528247