Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes

There are many factors that regulate the rate of synthesis of δ- aminolevulinate synthase (ALA-S), the enzyme which governs the rate-limiting step in heme biosynthesis. In rat hepatocytes, phenobarbital increases ALA-S gene transcription and dibutyryl cAMP potentiates this induction, whereas insulin...

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Autores principales: Varone, Cecilia Laura, Cánepa, Eduardo Tomás
Publicado: 1997
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rat
Acceso en línea:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v341_n2_p259_Varone
http://hdl.handle.net/20.500.12110/paper_00039861_v341_n2_p259_Varone
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spelling paper:paper_00039861_v341_n2_p259_Varone2023-06-08T14:25:03Z Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes Varone, Cecilia Laura Cánepa, Eduardo Tomás aminolevulinic acid synthase cAMP diacylglycerol gene expression hepatocytes phorbol esters protein kinase C 5 aminolevulinate synthase bucladesine cyclic AMP dioctanoin glucose heme insulin messenger RNA phenobarbital phorbol 13 acetate 12 myristate protein kinase C animal cell article controlled study enzyme activation gene expression regulation liver cell male nonhuman priority journal protein expression rat transcription regulation Animalia Canis familiaris There are many factors that regulate the rate of synthesis of δ- aminolevulinate synthase (ALA-S), the enzyme which governs the rate-limiting step in heme biosynthesis. In rat hepatocytes, phenobarbital increases ALA-S gene transcription and dibutyryl cAMP potentiates this induction, whereas insulin and glucose have the opposite effect. The present report provides evidence that protein kinase C (PKC) activation negatively influences ALA-S mRNA levels, as measured by Northern and slot-blot analysis. The addition of 1,2-dioctanoyl-sn-glycerol (DOG) or 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC activator that mimics diacylglycerol function, to cultures led to a significant decrease of both basal and phenobarbital-induced ALA-S mRNA levels in a dose-dependent manner. This TPA effect depends on the specific activation of PKC because the analog 4α-phorbol 12,13-diacetate, a nonstimulatory PKC phorbol ester, is unable to inhibit ALA-S mRNA. Furthermore, the effect of TPA is blocked by the PKC inhibitors staurosporine and calphostin C. Desensitization of the PKC pathway by prolonged exposure to TPA abolished the subsequent action of the phorbol ester. On the other hand, neither TPA nor DOG modified the half-life of ALA-S mRNA. The study of the combinatorial action of TPA and cAMP revealed that the inhibitory effect of TPA overcomes dibutyryl cAMP induction. Thus, these results indicate that PKC plays an essential role in regulating ALA-S expression, probably at a transcriptional level. Fil:Varone, C.L. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. Fil:Cánepa, E.T. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. 1997 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v341_n2_p259_Varone http://hdl.handle.net/20.500.12110/paper_00039861_v341_n2_p259_Varone
institution Universidad de Buenos Aires
institution_str I-28
repository_str R-134
collection Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic aminolevulinic acid synthase
cAMP
diacylglycerol
gene expression
hepatocytes
phorbol esters
protein kinase C
5 aminolevulinate synthase
bucladesine
cyclic AMP
dioctanoin
glucose
heme
insulin
messenger RNA
phenobarbital
phorbol 13 acetate 12 myristate
protein kinase C
animal cell
article
controlled study
enzyme activation
gene expression regulation
liver cell
male
nonhuman
priority journal
protein expression
rat
transcription regulation
Animalia
Canis familiaris
spellingShingle aminolevulinic acid synthase
cAMP
diacylglycerol
gene expression
hepatocytes
phorbol esters
protein kinase C
5 aminolevulinate synthase
bucladesine
cyclic AMP
dioctanoin
glucose
heme
insulin
messenger RNA
phenobarbital
phorbol 13 acetate 12 myristate
protein kinase C
animal cell
article
controlled study
enzyme activation
gene expression regulation
liver cell
male
nonhuman
priority journal
protein expression
rat
transcription regulation
Animalia
Canis familiaris
Varone, Cecilia Laura
Cánepa, Eduardo Tomás
Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
topic_facet aminolevulinic acid synthase
cAMP
diacylglycerol
gene expression
hepatocytes
phorbol esters
protein kinase C
5 aminolevulinate synthase
bucladesine
cyclic AMP
dioctanoin
glucose
heme
insulin
messenger RNA
phenobarbital
phorbol 13 acetate 12 myristate
protein kinase C
animal cell
article
controlled study
enzyme activation
gene expression regulation
liver cell
male
nonhuman
priority journal
protein expression
rat
transcription regulation
Animalia
Canis familiaris
description There are many factors that regulate the rate of synthesis of δ- aminolevulinate synthase (ALA-S), the enzyme which governs the rate-limiting step in heme biosynthesis. In rat hepatocytes, phenobarbital increases ALA-S gene transcription and dibutyryl cAMP potentiates this induction, whereas insulin and glucose have the opposite effect. The present report provides evidence that protein kinase C (PKC) activation negatively influences ALA-S mRNA levels, as measured by Northern and slot-blot analysis. The addition of 1,2-dioctanoyl-sn-glycerol (DOG) or 12-O-tetradecanoylphorbol 13-acetate (TPA), a PKC activator that mimics diacylglycerol function, to cultures led to a significant decrease of both basal and phenobarbital-induced ALA-S mRNA levels in a dose-dependent manner. This TPA effect depends on the specific activation of PKC because the analog 4α-phorbol 12,13-diacetate, a nonstimulatory PKC phorbol ester, is unable to inhibit ALA-S mRNA. Furthermore, the effect of TPA is blocked by the PKC inhibitors staurosporine and calphostin C. Desensitization of the PKC pathway by prolonged exposure to TPA abolished the subsequent action of the phorbol ester. On the other hand, neither TPA nor DOG modified the half-life of ALA-S mRNA. The study of the combinatorial action of TPA and cAMP revealed that the inhibitory effect of TPA overcomes dibutyryl cAMP induction. Thus, these results indicate that PKC plays an essential role in regulating ALA-S expression, probably at a transcriptional level.
author Varone, Cecilia Laura
Cánepa, Eduardo Tomás
author_facet Varone, Cecilia Laura
Cánepa, Eduardo Tomás
author_sort Varone, Cecilia Laura
title Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
title_short Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
title_full Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
title_fullStr Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
title_full_unstemmed Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
title_sort evidence that protein kinase c is involved in δ-aminolevulinate synthase expression in rat hepatocytes
publishDate 1997
url https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00039861_v341_n2_p259_Varone
http://hdl.handle.net/20.500.12110/paper_00039861_v341_n2_p259_Varone
work_keys_str_mv AT varonececilialaura evidencethatproteinkinasecisinvolvedindaminolevulinatesynthaseexpressioninrathepatocytes
AT canepaeduardotomas evidencethatproteinkinasecisinvolvedindaminolevulinatesynthaseexpressioninrathepatocytes
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