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Human adipose angiotensinogen gene expression and secretion are stimulated by cyclic AMP via increased DNA cyclic AMP responsive element binding activity

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Abstract

Components of the adipose renin-angiotensin system (RAS) have been suggested as providing a potential pathway linking obesity to hypertension. In adipose cells, the biological responses to β-adrenergic stimulation are mediated by an increase in intracellular cAMP. Because an association exists among body fat mass, hypertension, and increased sympathetic stimulation, we examined the influence of cAMP on angiotensinogen (ATG) expression and secretion in human adipose tissue and in parallel we studied the DNA binding activity of CRE transcriptional factors. A 24 h exposure to the cAMP analog 8Br-cAMP resulted in significant increases in ATG mRNA levels (+176 ±60%) and protein secretion (+40 ±27%). The ability of 8Br-cAMP to promote ATG gene expression was unaltered by H89, a protein kinase A inhibitor, because H89 perse was found to stimulate ATG mRNA levels and protein secretion. Moreover, 8Br-cAMP stimulated the specific CRE DNA binding activity (+115 ±14%) in human adipocyte nuclear extracts as assessed by electrophoretic mobility shift assays. These results indicate that cAMP upregulates in vitro ATG expression and secretion in human adipose tissue and that the induction in ATG mRNA levels appears to result, at least in part, from positive effects on the DNA binding activity of CRE transcription factors. Further studies are required to determine whether this regulatory pathway is activated in human obesity and to elucidate the importance of adipose ATG to the elevated blood pressure observed in this pathological state.

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Authors and Affiliations

  1. Laboratoire de Biochimie et de Biologie Moléculaire de la Faculté de Médecine Paris-Ile-de-France-Ouest, UPRES EA 2493, Université Versailles Saint Quentin en Yvelines, France

    Valérie Serazin, Esther Dos Santos, Mireille Morot & Yves Giudicelli

  2. Hôpital de Poissy, F78303, Poissy Cedex, France

    Valérie Serazin, Esther Dos Santos, Mireille Morot & Yves Giudicelli

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  1. Valérie Serazin
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  2. Esther Dos Santos
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  3. Mireille Morot
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  4. Yves Giudicelli
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Serazin, V., Santos, E.D., Morot, M. et al. Human adipose angiotensinogen gene expression and secretion are stimulated by cyclic AMP via increased DNA cyclic AMP responsive element binding activity. Endocr 25, 97–103 (2004). https://doi.org/10.1385/ENDO:25:2:097

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  • DOI: https://doi.org/10.1385/ENDO:25:2:097

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