Regulation of albumin gene expression in carbon tetrachloride-induced liver cell injury

• Published in: Kanzo Vol. 36; no. 5; pp. 289 - 295
• Main Authors: KUWAHATA, Masashi, OBARA, Hirohiko, KATO, Akinobu, OKA, Tatsuzo
• Format: Journal Article
• Language: Japanese
• Published: The Japan Society of Hepatology 1995
• ISSN: 0451-4203; 1881-3593
• DOI: 10.2957/kanzo.36.289

The control mechanism of albumin gene expression in carbon tetrachloride (CCl4)-induced liver damage was investigated. Rats were injected intraperitoneally with CCl4 (1.0ml/kg b.w.) and killed at various time intervals. The level of albumin mRNA in the liver, measured by Northern blot hybridization, was found to be 30%, 18% and 40% of the control value at 6, 12 and 24 hours after CCl4 administration, respectively. Since the transcription rate of albumin gene, measured by a nuclear run-on assay, was decreased by 50% at 12 hours, destabilization of albumin mRNA must have also occurred in the CCl4-poisoned liver. Gel mobility shift assay showed that DNA-binding activities of tissue-specific transcriptional factors, HNF1 and C/EBP, were decreased by 50% at 12 hours while Western blot assay indicated that the concentration of C/EBP was unchanged in CCl4 poisoning. These results suggest that the decrease in albumin gene expression in CCl4-induced liver injury is due to inactivation of tissue-specific transcriptional factors such as HNF1 and C/EBP and destabilization of albumin mRNA.