salubrinal and Chemical-and-Drug-Induced-Liver-Injury

To investigate the impact of alpha subunit of eukaryotic initiation factor 2 (eIF2α) phosphorylation on liver regeneration.. Male BALB/c mice were intraperitoneally injected with carbon tetrachloride (CCl4) 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.. CCl4 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.. In acute liver injury, inhibiting eIF2α dephosphorylation protects injured hepatocytes and reduces hepatocyte proliferation.

Topics: Animals; Apoptosis; Carbon Tetrachloride; Cell Proliferation; Chemical and Drug Induced Liver Injury; Cinnamates; Endoplasmic Reticulum Stress; Enzyme Inhibitors; Eukaryotic Initiation Factor-2; Hepatocytes; HSP40 Heat-Shock Proteins; Humans; Liver Regeneration; Male; Mice; Mice, Inbred BALB C; Phosphorylation; Thapsigargin; Thiourea