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Abstract:

By using tissue miniunits, protein kinase modulators, and topoisomerase inhibitors in short-term incubation (0-90 min) we studied (1) the role of protein phosphorylation in the immediate control of DNA replication in the developing rat cerebral cortex and (2) the mechanism of action for genistein- mediated DNA synthesis inhibition. Genistein decreased the DNA synthesis within less than 30 min. None of the other protein kinase inhibitors examined (herbimycin A, staurosporine, calphostin-C) or the protein phosphatase inhibitor sodium orthovanadate inhibited DNA synthesis and they did not affect the genistein-mediated inhibition. The selective topoisomerase inhibitors camptothecin and etoposide decreased the DNA synthesis to an extent similar to that of genistein and within less than 30 min. In addition, the effects of these substances on topoisomerase I and II were studied. Etoposide and genistein but not herbimycin A, staurosporine, or calphostin-C strongly inhibited the activity of topoisomerase II. Our results (1) strongly suggest that the net rate of DNA replication during the S phase of the cell cycle is independent of protein phosphorylation and (2) indicate that the early inhibitory effect of genistein on DNA synthesis is mediated by topoisomerase II inhibition rather than protein tyrosine kinase inhibition.

Registro:

Documento: Artículo
Título:Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex
Autor:Yakisich, J.S.; Sidén, A.; Vargas, V.I.; Eneroth, P.; Cruz, M.
Filiación:Applied Biochemistry, Clinical Research Center, Huddinge University Hospital, S-141 86 Huddinge, Sweden
Karolinska Institute, Huddinge University Hospital, Department of Neurology, S-141 86 Huddinge, Sweden
Fac. de Ciencias Exactas Y Naturales, Inst. Invest. Bioquimicas Fund. C., Buenos Aires, Argentina
Palabras clave:Cerebral cortex; DNA synthesis; Genistein; Protein kinases; Protein phosphorylation; Topoisomerases; calphostin C; camptothecin; DNA topoisomerase; DNA topoisomerase (ATP hydrolysing); DNA topoisomerase inhibitor; etoposide; genistein; herbimycin A; phosphoprotein phosphatase inhibitor; protein kinase inhibitor; staurosporine; animal tissue; article; brain cortex; cell cycle S phase; controlled study; DNA replication; DNA synthesis; DNA synthesis inhibition; enzyme activity; enzyme inhibition; newborn; nonhuman; priority journal; protein phosphorylation; rat
Año:1999
Volumen:159
Número:1
Página de inicio:164
Página de fin:176
DOI: http://dx.doi.org/10.1006/exnr.1999.7121
Título revista:Experimental Neurology
Título revista abreviado:Exp. Neurol.
ISSN:00144886
CODEN:EXNEA
CAS:calphostin C, 121263-19-2; camptothecin, 7689-03-4; DNA topoisomerase, 80449-01-0; DNA topoisomerase (ATP hydrolysing); etoposide, 33419-42-0, 433304-61-1; genistein, 446-72-0; herbimycin A, 70563-58-5; staurosporine, 62996-74-1
Registro:https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_00144886_v159_n1_p164_Yakisich

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Citas:

---------- APA ----------
Yakisich, J.S., Sidén, A., Vargas, V.I., Eneroth, P. & Cruz, M. (1999) . Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex. Experimental Neurology, 159(1), 164-176.
http://dx.doi.org/10.1006/exnr.1999.7121
---------- CHICAGO ----------
Yakisich, J.S., Sidén, A., Vargas, V.I., Eneroth, P., Cruz, M. "Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex" . Experimental Neurology 159, no. 1 (1999) : 164-176.
http://dx.doi.org/10.1006/exnr.1999.7121
---------- MLA ----------
Yakisich, J.S., Sidén, A., Vargas, V.I., Eneroth, P., Cruz, M. "Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex" . Experimental Neurology, vol. 159, no. 1, 1999, pp. 164-176.
http://dx.doi.org/10.1006/exnr.1999.7121
---------- VANCOUVER ----------
Yakisich, J.S., Sidén, A., Vargas, V.I., Eneroth, P., Cruz, M. Early effects of protein kinase modulators on DNA synthesis in rat cerebral cortex. Exp. Neurol. 1999;159(1):164-176.
http://dx.doi.org/10.1006/exnr.1999.7121