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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Autor principal: Varone, C.L
Otros Autores: Cánepa, E.T
Formato: Capítulo de libro
Lenguaje:Inglés
Publicado: Academic Press Inc. 1997
Acceso en línea:Registro en Scopus
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024 7 |2 scopus  |a 2-s2.0-0031570291 
024 7 |2 cas  |a 5 aminolevulinate synthase, 9037-14-3; bucladesine, 16980-89-5, 362-74-3; cyclic AMP, 60-92-4; dioctanoin, 36354-80-0; glucose, 50-99-7, 84778-64-3; heme, 14875-96-8; insulin, 9004-10-8; phenobarbital, 50-06-6, 57-30-7, 8028-68-0; phorbol 13 acetate 12 myristate, 16561-29-8; protein kinase C, 141436-78-4 
040 |a Scopus  |b spa  |c AR-BaUEN  |d AR-BaUEN 
030 |a ABBIA 
100 1 |a Varone, C.L. 
245 1 0 |a Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes 
260 |b Academic Press Inc.  |c 1997 
270 1 0 |m Canepa, E.T.; Departamento de Quimica Biologica, Ciudad Universitaria, Pabellon II, 4 piso, 1428 Buenos Aires, Argentina 
506 |2 openaire  |e Política editorial 
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520 3 |a 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.  |l eng 
536 |a Detalles de la financiación: Universidad de Buenos Aires 
536 |a Detalles de la financiación: 1This work was supported by research grants from the Universi-dad de Buenos Aires. 2To whom correspondence should be addressed at Departamento de QuõBmica BioloÂgica, Ciudad Universitaria, PabelloÂn II, 4° piso, 
593 |a Lab. de Regulacion de la E., Depto. de Quim. Biológica, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina 
593 |a Depto. de Quim. Biológica, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina 
690 1 0 |a AMINOLEVULINIC ACID SYNTHASE 
690 1 0 |a CAMP 
690 1 0 |a DIACYLGLYCEROL 
690 1 0 |a GENE EXPRESSION 
690 1 0 |a HEPATOCYTES 
690 1 0 |a PHORBOL ESTERS 
690 1 0 |a PROTEIN KINASE C 
690 1 0 |a 5 AMINOLEVULINATE SYNTHASE 
690 1 0 |a BUCLADESINE 
690 1 0 |a CYCLIC AMP 
690 1 0 |a DIOCTANOIN 
690 1 0 |a GLUCOSE 
690 1 0 |a HEME 
690 1 0 |a INSULIN 
690 1 0 |a MESSENGER RNA 
690 1 0 |a PHENOBARBITAL 
690 1 0 |a PHORBOL 13 ACETATE 12 MYRISTATE 
690 1 0 |a PROTEIN KINASE C 
690 1 0 |a ANIMAL CELL 
690 1 0 |a ARTICLE 
690 1 0 |a CONTROLLED STUDY 
690 1 0 |a ENZYME ACTIVATION 
690 1 0 |a GENE EXPRESSION REGULATION 
690 1 0 |a LIVER CELL 
690 1 0 |a MALE 
690 1 0 |a NONHUMAN 
690 1 0 |a PRIORITY JOURNAL 
690 1 0 |a PROTEIN EXPRESSION 
690 1 0 |a RAT 
690 1 0 |a TRANSCRIPTION REGULATION 
690 1 0 |a ANIMALIA 
690 1 0 |a CANIS FAMILIARIS 
700 1 |a Cánepa, E.T. 
773 0 |d Academic Press Inc., 1997  |g v. 341  |h pp. 259-266  |k n. 2  |p ARCH. BIOCHEM. BIOPHYS.  |x 00039861  |w (AR-BaUEN)CENRE-1377  |t Archives of Biochemistry and Biophysics 
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