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Estrogen modulates ClC-2 chloride channel gene expression in rat kidney

  • Ion Channels, Transporters
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Abstract

ClC-2 is a CLC family member of chloride channels sensitive to changes in cell volume, pH and voltage. The ClC-2 is widely distributed along the nephron although in the kidney its role still not well understood. Aldosterone studies suggest that ClC-2 expression in the kidney may be hormonally regulated. To explore the possibility that estrogen control ClC-2 expression, we investigated whether its expression changed in the kidney of female Wistar rats subjected to ovariectomy with or without near-physiological or high doses of 17β-estradiol benzoate treatment for 10 days. Total RNA isolated from rat kidney and dissected nephron segments was analyzed by ribonuclease protection assay and/or a semi-quantitative RT-PCR. The renal ClC-2 protein expression was analyzed by Western blot. The decreased renal expression of ClC-2 mRNA and protein observed in ovariectomized rats was restored to control levels after treatment with low doses of estradiol. Higher dose estradiol lead to an even greater increase in ClC-2 mRNA and protein expression. This change in overall expression was shown to be caused by the modulation of ClC-2 mRNA expression in the proximal tubule. These results suggest that ClC-2 may be involved in estrogen-induced Cl− transport in rat kidney.

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Acknowledgements

The present work was supported by grants from NIH (HL47122 and DK 32753), Programa de Apoio ao Desenvolvimento Cientifico e Tecnológico (PADCIII), Fundação José Bonifàcio (FUJB), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (FAPERJ), Fundação de Amparo à Pesquisa do Estado de Sào Paulo (FAPESP), Financiadora de Estudos e Projetos (FINEP) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPQ).

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Authors and Affiliations

  1. Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 21949-900, Rio de Janeiro, Brazil

    Danielle S. Nascimento, Carlos U. Reis, Regina C. Goldenberg, Tânia M. Ortiga-Carvalho, Carmen C. Pazos-Moura & Marcelo M. Morales

  2. Department of Physiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

    William B. Guggino

  3. Department of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA

    Sandra E. Guggino

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  1. Danielle S. Nascimento
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  2. Carlos U. Reis
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  3. Regina C. Goldenberg
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  4. Tânia M. Ortiga-Carvalho
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  5. Carmen C. Pazos-Moura
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  6. Sandra E. Guggino
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  7. William B. Guggino
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  8. Marcelo M. Morales
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Correspondence to Marcelo M. Morales.

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Nascimento, D.S., Reis, C.U., Goldenberg, R.C. et al. Estrogen modulates ClC-2 chloride channel gene expression in rat kidney. Pflugers Arch - Eur J Physiol 446, 593–599 (2003). https://doi.org/10.1007/s00424-003-1095-y

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