TY - JOUR
T1 - Regulation of rat alcohol-dehydrogenase by cyclic AMP in primary hepatocyte culture
AU - Potter, James J.
AU - Macdougald, Ormond A.
AU - Mezey, Esteban
PY - 1995/8/20
Y1 - 1995/8/20
N2 - Alcohol dehydrogenase (ADH) is enhanced separately by epinephrine and by glucagon in primary rat hepatocyte culture. This study determined whether cyclic AMP, a common mediator for some of the actions of the above hormones, increases ADH. Administration of theophylline, a cyclic AMP phosphodiesterase inhibitor which increases endogenous cyclic AMP, in a dose of 100 mg/kg to rats for 5 days, increased ADH activity. Dibutyryl cyclic AMP (10 μM) added to primary hepatocytes in culture increased ADH mRNA and ADH activity at 12 and 24 h, respectively, after its addition. The increase in ADH mRNA was preceded by an increase in the expression of C/EBPβ mRNA and in C/EBPβ protein. Dibutyryl cyclic AMP, in transient transfection experiments of primary rat hepatocyte culture, activated an ADH promoter gene construct containing the C/EBP binding site, but failed to activate a construct containing a 4-bp mutation at this site. These results show that cyclic AMP induces ADH and suggests that this effect is mediated by C/EBPβ binding to the C/EBP site. The previously demonstrated induction of ADH by epinephrine and glucagon may be mediated by a common pathway via an increase in cyclic AMP.
AB - Alcohol dehydrogenase (ADH) is enhanced separately by epinephrine and by glucagon in primary rat hepatocyte culture. This study determined whether cyclic AMP, a common mediator for some of the actions of the above hormones, increases ADH. Administration of theophylline, a cyclic AMP phosphodiesterase inhibitor which increases endogenous cyclic AMP, in a dose of 100 mg/kg to rats for 5 days, increased ADH activity. Dibutyryl cyclic AMP (10 μM) added to primary hepatocytes in culture increased ADH mRNA and ADH activity at 12 and 24 h, respectively, after its addition. The increase in ADH mRNA was preceded by an increase in the expression of C/EBPβ mRNA and in C/EBPβ protein. Dibutyryl cyclic AMP, in transient transfection experiments of primary rat hepatocyte culture, activated an ADH promoter gene construct containing the C/EBP binding site, but failed to activate a construct containing a 4-bp mutation at this site. These results show that cyclic AMP induces ADH and suggests that this effect is mediated by C/EBPβ binding to the C/EBP site. The previously demonstrated induction of ADH by epinephrine and glucagon may be mediated by a common pathway via an increase in cyclic AMP.
KW - Alcohol dehydrogenase
KW - C/EBP/β
KW - C/EBPα
KW - Dibutyryl cAMP
KW - Hepatocyte culture
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U2 - 10.1006/abbi.1995.1402
DO - 10.1006/abbi.1995.1402
M3 - Article
C2 - 7646058
AN - SCOPUS:0029129531
SN - 0003-9861
VL - 321
SP - 329
EP - 335
JO - Archives of Biochemistry and Biophysics
JF - Archives of Biochemistry and Biophysics
IS - 2
ER -