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Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury

AIM: To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration. METHODS: Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl(4)) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsig...

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Autores principales: Chen, Guimei, Yang, Xuemei, He, Yihuai, Tang, Yongjing, Tian, Rendong, Huang, Wenge, Chen, Huan, Yang, Fangwan, Li, Ying, Lin, Shide
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Croatian Medical Schools 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952896/
https://www.ncbi.nlm.nih.gov/pubmed/31894919
http://dx.doi.org/10.3325/cmj.2019.60.532
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author Chen, Guimei
Yang, Xuemei
He, Yihuai
Tang, Yongjing
Tian, Rendong
Huang, Wenge
Chen, Huan
Yang, Fangwan
Li, Ying
Lin, Shide
author_facet Chen, Guimei
Yang, Xuemei
He, Yihuai
Tang, Yongjing
Tian, Rendong
Huang, Wenge
Chen, Huan
Yang, Fangwan
Li, Ying
Lin, Shide
author_sort Chen, Guimei
collection PubMed
description AIM: To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration. METHODS: Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl(4)) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsigargin to induce endoplasmic reticulum (ER) stress. Salubrinal, integrated stress response inhibitor (ISRIB), and DnaJC3 overexpression were used to alter eIF2α phosphorylation levels. RESULTS: CCl(4) administration induced significant ER stress and eIF2α phosphorylation, and increased hepatocyte proliferation proportionally to the extent of injury. Inhibiting eIF2α dephosphorylation with salubrinal pretreatment significantly mitigated liver injury and hepatocyte proliferation. In LO2 cells, thapsigargin induced significant eIF2α phosphorylation and inhibited proliferation. Inhibiting eIF2α dephosphorylation partly restored cell proliferation during ER stress. CONCLUSIONS: In acute liver injury, inhibiting eIF2α dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation.
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spelling pubmed-69528962020-01-16 Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury Chen, Guimei Yang, Xuemei He, Yihuai Tang, Yongjing Tian, Rendong Huang, Wenge Chen, Huan Yang, Fangwan Li, Ying Lin, Shide Croat Med J Reasearch Article AIM: To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration. METHODS: Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl(4)) to induce liver injury. Human hepatocyte LO2 cells were incubated with thapsigargin to induce endoplasmic reticulum (ER) stress. Salubrinal, integrated stress response inhibitor (ISRIB), and DnaJC3 overexpression were used to alter eIF2α phosphorylation levels. RESULTS: CCl(4) administration induced significant ER stress and eIF2α phosphorylation, and increased hepatocyte proliferation proportionally to the extent of injury. Inhibiting eIF2α dephosphorylation with salubrinal pretreatment significantly mitigated liver injury and hepatocyte proliferation. In LO2 cells, thapsigargin induced significant eIF2α phosphorylation and inhibited proliferation. Inhibiting eIF2α dephosphorylation partly restored cell proliferation during ER stress. CONCLUSIONS: In acute liver injury, inhibiting eIF2α dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation. Croatian Medical Schools 2019-12 /pmc/articles/PMC6952896/ /pubmed/31894919 http://dx.doi.org/10.3325/cmj.2019.60.532 Text en Copyright © 2019 by the Croatian Medical Journal. All rights reserved. http://creativecommons.org/licenses/by/2.5/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Reasearch Article
Chen, Guimei
Yang, Xuemei
He, Yihuai
Tang, Yongjing
Tian, Rendong
Huang, Wenge
Chen, Huan
Yang, Fangwan
Li, Ying
Lin, Shide
Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title_full Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title_fullStr Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title_full_unstemmed Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title_short Inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
title_sort inhibiting alpha subunit of eukaryotic initiation factor 2 dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation in acute liver injury
topic Reasearch Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6952896/
https://www.ncbi.nlm.nih.gov/pubmed/31894919
http://dx.doi.org/10.3325/cmj.2019.60.532
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