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Differential effects of doxorubicin on atrial natriuretic peptide expression in vivo and in vitro
Rahman, Asim; Alam, Mahood; Rao, Sudha; Cai, Lin; Clark, Luther T; Shafiq, Sayid; Siddiqui, M. A. Q.
  • Rahman, Asim; State University of New York. Division of Cardiology. New York. US
  • Alam, Mahood; State University of New York. Center of Cardiovascular and Muscle Research. New York. US
  • Rao, Sudha; State University of New York. Division of Pediatry Cardiology. New York. US
  • Cai, Lin; State University of New York. Department of Anatomy and Cell Biology. New York. US
  • Clark, Luther T; State University of New York. Center of Cardiovascular and Muscle Research. New York. US
  • Shafiq, Sayid; State University of New York. Department of Neurology. New York. US
  • Siddiqui, M. A. Q; State University of New York. Center of Cardiovascular and Muscle Research. New York. US
Biol. Res ; 34(3/4): 195-206, 2001. ilus
Artigo em Inglês | LILACS | ID: lil-303883
ABSTRACT
Doxorubicin (Dox) is a potent anti-cancer agent with cardiotoxic side-effects but the mechanism of its cardiotoxicity and its effect on expression of the vasoactive atrial natriuretic peptide (ANP), an important marker for cardiac hypertrophy, are little understood. The present study examined Dox-induced changes in vivo in hearts of 6 mongrel dogs and 5 Sprague-Dawley rats and in vitro in cardiac cultures of neonatal rats. Quantitative RT-PCR analysis using gamma 32-p labeled primers for beta-actin, phospholamban (PLB) and ANP showed a selective 5-fold increase of ANP mRNA in Dox-treated dog hearts in comparison to controls. Similarly, northern analysis of GAPD, beta-actin, cardiac alpha-actin and ANP gave a selective 4.5-fold increase in ANP transcripts in Dox-treated rat hearts. On the other hand, there was a selective decrease (approximately 39 percent) of ANP transcripts in Dox-treated cardiac cultures relative to controls. Immunohistochemistry localized the ANP changes both in tissue sections and in cultures to the cardiomyocytes. The data clearly showed that Dox selectively increases ANP expression in dog and rat hearts in absence of cardiocyte hypertrophy but selectively decreases it in cardiac cultures. This differential effect of Dox on cardiocytes in vivo and in vitro should be a useful parameter for studies of transcriptional control of ANP expression.
Assuntos
Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Doxorrubicina / Fator Natriurético Atrial / Cardiopatias / Antineoplásicos Limite: Animais Idioma: Inglês Revista: Biol. Res Assunto da revista: Biologia Ano de publicação: 2001 Tipo de documento: Artigo País de afiliação: Estados Unidos Instituição/País de afiliação: State University of New York/US

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Texto completo: DisponíveL Índice: LILACS (Américas) Assunto principal: Doxorrubicina / Fator Natriurético Atrial / Cardiopatias / Antineoplásicos Limite: Animais Idioma: Inglês Revista: Biol. Res Assunto da revista: Biologia Ano de publicação: 2001 Tipo de documento: Artigo País de afiliação: Estados Unidos Instituição/País de afiliação: State University of New York/US