Regulation of albumin gene expression in carbon tetrachloride-induced liver cell injury
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,...
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| Published in | Kanzo Vol. 36; no. 5; pp. 289 - 295 |
|---|---|
| Main Authors | , , , |
| Format | Journal Article |
| Language | Japanese |
| Published |
The Japan Society of Hepatology
1995
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| Online Access | Get full text |
| ISSN | 0451-4203 1881-3593 |
| DOI | 10.2957/kanzo.36.289 |
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| Abstract | 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. |
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| AbstractList | 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. |
| Author | OBARA, Hirohiko KATO, Akinobu KUWAHATA, Masashi OKA, Tatsuzo |
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| References | 5) Zern MA, Chakraborty PR, Ruiz-Opazo N, et al: Development chronic ethanol administration on hepatic protein synthesis. Hepatology 3: 317-322, 1983 9) Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chlorofom extraction. Anal Biochem 162: 156-159, 1987 1) Ozaki I, Motomura M, Setoguchi Y, et al: Albumin mRNA expression in human liver disease and its correlation to serum albumin concentration. Gastroenterol Jpn 26: 472-476, 1991 12) Chodosh LA: Mobility shift DNA-binding assay using gel electrophoresis. Current Protocols Molecular Biology 12.2.1-12.2.10, 1990 3) Panduro A, Shalaby F, Biempical L, et al: Changes in Albumin, α-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis. 8 (2): 259-266, 1988 7) Cereghini S, Raymondjean M, Carranca AG, et al: Factors involved in control of tissuespecific expression of albumin gene. Cell 50: 627-638, 1987 11) Nawa K, Nakamura T, Kumatori A, et al: Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes. J Biol Chem 261: 16883-16888, 1986 15) Peavy DE, Taylor JM, Jefferson LS: Time course of changes in albumin synthesis and mRNA in diabetic and insulin-treated diabetic rats. Am J Physiol 248: E656-E663, 1985 8) Maire P, Wuarin J, Schibler U: The role of cis-acting promoter elements in tissue-specific albumin gene expression. Science 244: 343-346, 1989 2) Panduro A, Shalaby F, Weiner FR, et al: Transcriptional switch from albumin to α-fetoprotein and changes in transcription of others genes during carbon tetrachloride induced liver regeneration. Biochemistry 25: 1414-1420, 1986 4) Princen JMG, Neuwenhaizen W, Mol-Back GHBM, et al: Direct evidence for transcriptional control of fibrinogen and albumin synthesis in rat liver during acute response. Biochem Biophys Res Commun 102: 717-723, 1981 14) Oka T, Sasakawa T, Komori N, et al: Developmental changes in the expression of HMG 2a protein. FEBS Lett 316: 20-22, 1993 13) Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 227: 680-685, 1970 6) Zern MA, Saber MA, Shafritz DA: Changes in the molecular mechanisms of hepatic protein synthesis induced by schistosome infection in mice. Biochemistry 8: 259-266, 1983 10) Thomas PS: Hybridization of denatured RNA transferred or dottred to nitrocellulose paper. Methods Enzymol 100: 255-266, 1983 |
| References_xml | – reference: 6) Zern MA, Saber MA, Shafritz DA: Changes in the molecular mechanisms of hepatic protein synthesis induced by schistosome infection in mice. Biochemistry 8: 259-266, 1983 – reference: 7) Cereghini S, Raymondjean M, Carranca AG, et al: Factors involved in control of tissuespecific expression of albumin gene. Cell 50: 627-638, 1987 – reference: 15) Peavy DE, Taylor JM, Jefferson LS: Time course of changes in albumin synthesis and mRNA in diabetic and insulin-treated diabetic rats. Am J Physiol 248: E656-E663, 1985 – reference: 1) Ozaki I, Motomura M, Setoguchi Y, et al: Albumin mRNA expression in human liver disease and its correlation to serum albumin concentration. Gastroenterol Jpn 26: 472-476, 1991 – reference: 11) Nawa K, Nakamura T, Kumatori A, et al: Glucocorticoid-dependent expression of the albumin gene in adult rat hepatocytes. J Biol Chem 261: 16883-16888, 1986 – reference: 10) Thomas PS: Hybridization of denatured RNA transferred or dottred to nitrocellulose paper. Methods Enzymol 100: 255-266, 1983 – reference: 13) Laemmli UK: Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature (London) 227: 680-685, 1970 – reference: 14) Oka T, Sasakawa T, Komori N, et al: Developmental changes in the expression of HMG 2a protein. FEBS Lett 316: 20-22, 1993 – reference: 3) Panduro A, Shalaby F, Biempical L, et al: Changes in Albumin, α-fetoprotein and collagen gene transcription in CCl4-induced hepatic fibrosis. 8 (2): 259-266, 1988 – reference: 9) Chomczynski P, Sacchi N: Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chlorofom extraction. Anal Biochem 162: 156-159, 1987 – reference: 12) Chodosh LA: Mobility shift DNA-binding assay using gel electrophoresis. Current Protocols Molecular Biology 12.2.1-12.2.10, 1990 – reference: 2) Panduro A, Shalaby F, Weiner FR, et al: Transcriptional switch from albumin to α-fetoprotein and changes in transcription of others genes during carbon tetrachloride induced liver regeneration. Biochemistry 25: 1414-1420, 1986 – reference: 5) Zern MA, Chakraborty PR, Ruiz-Opazo N, et al: Development chronic ethanol administration on hepatic protein synthesis. Hepatology 3: 317-322, 1983 – reference: 4) Princen JMG, Neuwenhaizen W, Mol-Back GHBM, et al: Direct evidence for transcriptional control of fibrinogen and albumin synthesis in rat liver during acute response. Biochem Biophys Res Commun 102: 717-723, 1981 – reference: 8) Maire P, Wuarin J, Schibler U: The role of cis-acting promoter elements in tissue-specific albumin gene expression. Science 244: 343-346, 1989 |
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