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Stress granules inhibit endoplasmic reticulum stress-mediated apoptosis during hypoxia-induced injury in acute liver failure
BACKGROUND: Stress granules (SGs) could be formed under different stimulation to inhibit cell injury. AIM: To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure (ALF) by reducing endoplasmic reticulum stress (ERS) mediated apoptosis. METHODS: The...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Baishideng Publishing Group Inc
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10011964/ https://www.ncbi.nlm.nih.gov/pubmed/36925453 http://dx.doi.org/10.3748/wjg.v29.i8.1315 |
Sumario: | BACKGROUND: Stress granules (SGs) could be formed under different stimulation to inhibit cell injury. AIM: To investigate whether SGs could protect hepatocytes from hypoxia-induced damage during acute liver failure (ALF) by reducing endoplasmic reticulum stress (ERS) mediated apoptosis. METHODS: The agonist of SGs, arsenite (Ars) was used to intervene hypoxia-induced hepatocyte injury cellular model and ALF mice models. Further, the siRNA of activating transcription factor 4 (ATF4) and SGs inhibitor anisomycin was then used to intervene in cell models. RESULTS: With the increase of hypoxia time from 4 h to 12 h, the levels of HIF-1α, ERS and apoptosis gradually increased, and the expression of SGs marker G3BP1 and TIA-1 was increased and then decreased. Compared with the hypoxia cell model group and ALF mice model, the levels of HIF-1α, apoptosis and ERS were increased in the Ars intervention group. After siRNA-ATF4 intervention, the level of SGs in cells increased, and the levels of HIF-1α, ERS and apoptosis decreased. Compared with the siRNA-ATF4 group, the levels of G3BP1 in the siRNA-ATF4+anisomycin group were decreased, and the levels of HIF-1α, ERS and apoptosis were increased. Moreover, compared with the ALF group, the degree of liver injury and liver function, the levels of HIF-1α, ERS and apoptosis in the Ars intervention group were decreased, the level of SGs was increased. CONCLUSION: SGs could protect hepatocytes from hypoxia-induced damage during ALF by reducing ERS-mediated apoptosis. |
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