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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.


Documento: Artículo
Título:Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes
Autor:Varone, C.L.; Cánepa, E.T.
Filiación:Lab. de Regulacion de la E., Depto. de Quim. Biológica, Universidad de Buenos Aires, 1428 Buenos Aires, Argentina
Depto. de Quim. Biológica, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina
Palabras clave: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
Página de inicio:259
Página de fin:266
Título revista:Archives of Biochemistry and Biophysics
Título revista abreviado:ARCH. BIOCHEM. BIOPHYS.
CAS: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


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---------- APA ----------
Varone, C.L. & Cánepa, E.T. (1997) . Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes. Archives of Biochemistry and Biophysics, 341(2), 259-266.
---------- CHICAGO ----------
Varone, C.L., Cánepa, E.T. "Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes" . Archives of Biochemistry and Biophysics 341, no. 2 (1997) : 259-266.
---------- MLA ----------
Varone, C.L., Cánepa, E.T. "Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes" . Archives of Biochemistry and Biophysics, vol. 341, no. 2, 1997, pp. 259-266.
---------- VANCOUVER ----------
Varone, C.L., Cánepa, E.T. Evidence that protein kinase C is involved in δ-aminolevulinate synthase expression in rat hepatocytes. ARCH. BIOCHEM. BIOPHYS. 1997;341(2):259-266.