Abstract:
Background: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in enhanced adrenocorticotropin (ACTH) and serum glucocorticoid levels, has been described in patients with diabetes mellitus and in animal models of this disease; however, altered steroid production by adrenocortical cells could result from local changes triggered by increased reactive oxygen species (ROS), induced in turn by chronic hyperglycaemia. Experiments were designed (1) to analyse the effects of incubating murine adrenocortical cells in hyperglycaemic media on the generation of oxidative stress, on steroid synthesis and on its modulation by the activity of haeme oxygenase (HO); and (2) to evaluate the effect of antioxidant treatment on these parameters. Methods: Y1 cells were incubated for 7 days with either normal or high glucose (HG, 30 mmol/L) concentrations, with or without antioxidant treatment. Parameters of oxidative stress and expression levels of haeme oxygenase-1 (HO-1), nitrite levels, L-arginine uptake and progesterone production were determined. Results: HG augmented ROS and lipoperoxide production, decreasing glutathione (GSH) levels and increasing antioxidant enzymes and HO-1 expression. Basal progesterone production was reduced, while a higher response to ACTH was observed in HG-treated cells. The increase in HO-1 expression and the effects on basal steroid production were abolished by antioxidant treatment. Inhibition of HO activity increased basal and ACTH-stimulated steroid release. Similar results were obtained by HO-1 gene silencing while the opposite effect was observed in Y1 cells overexpressing HO-1. Conclusions?: HG induces oxidative stress and affects steroid production in adrenal cells; the involvement of HO activity in the modulation of steroidogenesis in Y1 cells is postulated. Copyright © 2009 John Wiley & Sons, Ltd.
Registro:
Documento: |
Artículo
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Título: | High glucose-induced changes in steroid production in adrenal cells |
Autor: | Astort, F.; Repetto, E.M.; Martínez Calejman, C.; Cipelli, J.M.; Sánchez, R.; Di Gruccio, J.M.; Mercau, M.; Pignataro, O.P.; Arias, P.; Cymeryng, C.B. |
Filiación: | Departamento de Bioquímica Humana, Universidad de Buenos Aires, CEFYBO (CONICET), Paraguay 2155 5o, (C1121ABG) Buenos Aires, Argentina Departamento de Química Biológica, Facultad de Ciencias Exactas Y Naturales, Universidad de Buenos Aires, V. de Obligado 2490, (C1428ADN) Buenos Aires, Argentina Departamento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, Paraguay 2155 7o, (C1121ABG) Buenos Aires, Argentina
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Palabras clave: | Adrenocortical cells; Antioxidants; Haeme oxygenase-1; High glucose; Nitric oxide; Oxidative stress; Steroids; arginine; corticotropin; glucose; glutathione; heme oxygenase 1; lipid peroxide; nitrite; progesterone; reactive oxygen metabolite; arginine; glucose; heme oxygenase; nitrite; progesterone; reactive oxygen metabolite; thiobarbituric acid reactive substance; adrenal cortex cell; animal cell; article; controlled study; enzyme activity; enzyme inhibition; gene silencing; hormone response; hyperglycemia; mouse; nonhuman; nucleotide sequence; oxidative stress; priority journal; progesterone synthesis; protein expression; rat; steroidogenesis; analysis of variance; animal; cell clone; cell culture; comparative study; cytology; dose response; genetic transfection; human; metabolism; nonparametric test; oxidative stress; physiology; zona fasciculata; Analysis of Variance; Animals; Arginine; Cells, Cultured; Clone Cells; Dose-Response Relationship, Drug; Glucose; Heme Oxygenase (Decyclizing); Humans; Hyperglycemia; Mice; Nitrites; Oxidative Stress; Progesterone; Rats; Reactive Oxygen Species; Statistics, Nonparametric; Thiobarbituric Acid Reactive Substances; Transfection; Zona Fasciculata |
Año: | 2009
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Volumen: | 25
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Número: | 5
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Página de inicio: | 477
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Página de fin: | 486
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DOI: |
http://dx.doi.org/10.1002/dmrr.978 |
Título revista: | Diabetes/Metabolism Research and Reviews
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Título revista abreviado: | Diabetes Metab. Res. Rev.
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ISSN: | 15207552
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CODEN: | DMRRF
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CAS: | arginine, 1119-34-2, 15595-35-4, 7004-12-8, 74-79-3; corticotropin, 11136-52-0, 9002-60-2, 9061-27-2; glucose, 50-99-7, 84778-64-3; glutathione, 70-18-8; nitrite, 14797-65-0; progesterone, 57-83-0; heme oxygenase, 9059-22-7; Arginine, 74-79-3; Glucose, 50-99-7; Heme Oxygenase (Decyclizing), 1.14.99.3; Nitrites; Progesterone, 57-83-0; Reactive Oxygen Species; Thiobarbituric Acid Reactive Substances
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Registro: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_15207552_v25_n5_p477_Astort |
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Citas:
---------- APA ----------
Astort, F., Repetto, E.M., Martínez Calejman, C., Cipelli, J.M., Sánchez, R., Di Gruccio, J.M., Mercau, M.,..., Cymeryng, C.B.
(2009)
. High glucose-induced changes in steroid production in adrenal cells. Diabetes/Metabolism Research and Reviews, 25(5), 477-486.
http://dx.doi.org/10.1002/dmrr.978---------- CHICAGO ----------
Astort, F., Repetto, E.M., Martínez Calejman, C., Cipelli, J.M., Sánchez, R., Di Gruccio, J.M., et al.
"High glucose-induced changes in steroid production in adrenal cells"
. Diabetes/Metabolism Research and Reviews 25, no. 5
(2009) : 477-486.
http://dx.doi.org/10.1002/dmrr.978---------- MLA ----------
Astort, F., Repetto, E.M., Martínez Calejman, C., Cipelli, J.M., Sánchez, R., Di Gruccio, J.M., et al.
"High glucose-induced changes in steroid production in adrenal cells"
. Diabetes/Metabolism Research and Reviews, vol. 25, no. 5, 2009, pp. 477-486.
http://dx.doi.org/10.1002/dmrr.978---------- VANCOUVER ----------
Astort, F., Repetto, E.M., Martínez Calejman, C., Cipelli, J.M., Sánchez, R., Di Gruccio, J.M., et al. High glucose-induced changes in steroid production in adrenal cells. Diabetes Metab. Res. Rev. 2009;25(5):477-486.
http://dx.doi.org/10.1002/dmrr.978