Inhibition of eIF2α Dephosphorylation Protects Hepatocytes from Apoptosis by Alleviating ER Stress in Acute Liver Injury

Figure 3

Inhibition of eIF2α dephosphorylation mitigates CCl₄-induced apoptosis and liver injury in mice. Male BALB/c mice were pretreated with a vehicle (DMSO+PBS, control), salubrinal, ISRIB, or PBA for 2 h or with the recombinant AAV8 that expressed DnaJC3 for 4 weeks and then injected with olive oil or CCl₄ for another 24 h. (a) Levels of intrahepatic p-eIF2α, ATF4, and cleaved caspase-3 in control, salubrinal, ISRIB, PBA, and CCl₄ groups. (b) Salubrinal, ISRIB, PBA, or (c) the overexpressed DnaJC3 altered the levels of DnaJC3, p-eIF2α, AFT4, and cleaved caspase-3 in the liver. (d) Immunohistochemistry staining of cleaved caspase-3 expression in the liver (magnification ×100). (e) Kinetic serum ALT levels among different groups of mice. (f) Liver histology (magnification ×100). Hash sign indicates the necrotic area. Representative blots, immunohistochemistry, and histology from four independent experiments are shown. Histograms represent of four independent experiments (-10, total ). , versus the control group. ^† versus the CCl₄ or AAV8+CCl₄ group.

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