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. 1997 Oct;151(4):891–896.

Inhibition of NF-kappa B activity induces apoptosis in murine hepatocytes.

R E Bellas 1, M J FitzGerald 1, N Fausto 1, G E Sonenshein 1
PMCID: PMC1858057  PMID: 9327720

Abstract

Recently we have demonstrated that inhibition of the nuclear factor (NF)-kappa B/Rel family of transcription factors induces apoptosis of B cells. Interestingly, mice lacking the relA gene encoding the p65 subunit of NF-kappa B exhibit embryonic lethality at days 15 to 16 of gestation, accompanied by massive destruction of liver via apoptosis. To determine whether p65 protein plays a direct role in hepatocyte survival, we employed a nontransformed murine hepatocyte (NMH) cell line, which maintains to a high degree the differentiated hepatocyte phenotype. Exponentially growing NMH cells were found to possess a constitutive level of functional classical (p50/p65) NF-kappa B as assayed by electrophoretic mobility shift analysis, antibody supershift, and transient transfection assays. Treatment of NMH cells with the proteasome inhibitor lactacystin, which prevents degradation of the NF-kappa B inhibitor proteins I kappa B, induced apoptosis. Direct inhibition of the endogenous NF-kappa B activity by microinjection of NMH cells with purified specific inhibitor I kappa B-alpha-glutathione-S-transferase fusion protein or an antibody against p65 protein induced apoptosis. These findings suggest that expression of NF-kappa B/Rel activity in murine hepatocytes acts directly to promote survival of these cells and suggest that apoptosis observed in hepatocytes of mice lacking relA is a direct effect of p65 deficiency.

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Selected References

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