Tissue-specific expression of the human brain natriuretic peptide gene in cardiac myocytes

Hypertension
M C LaPointeD G Gardner

Abstract

Brain natriuretic peptide (BNP) is a cardiac hormone constitutively expressed in the adult heart. To identify the cis-acting elements involved in regulation of the human BNP gene, we subcloned the full-length promoter (-1818 to +100) and deletions thereof upstream from a luciferase reporter gene and transiently transfected them into primary cultures of neonatal rat atrial and ventricular myocytes and myocardial fibroblasts. Luciferase activity of the full-length construct was higher in ventricular (39064 +/- 8488 relative light units, N=11) and atrial (11225 +/- 1907, N=17) myocytes than myocardial fibroblasts (329 +/- 113, n=5). Maximal promoter activity in ventricular and atrial myocytes was maintained by sequences positioned between -1818 and -1283 relative to the transcription start site. Deletion to -1175 resulted in a decrease, whereas further deletion to -500 effected an increase in reporter activity in both cell types. In ventricular and atrial myocytes, deletion from -500 to -40 reduced luciferase activity 20-fold and 2-fold, respectively, whereas in myocardial fibroblasts, deletion to -40 upregulated the BNP promoter 2-fold. Of note, deleting 16 bp between -127 and -111 reduced luciferase activity 7-fold and 4-fold in...Continue Reading

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Citations

Feb 6, 2004·Pharmacology & Therapeutics·Savio P D'SouzaGary F Baxter
Apr 29, 1999·Domestic Animal Endocrinology·G D AitkenV A Cameron
Aug 5, 2011·Canadian Journal of Physiology and Pharmacology·Elina KoivistoHeikki Ruskoaho
Nov 3, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Quan HeMargot C LaPointe
Oct 22, 2008·Hypertension·Songcang ChenDavid G Gardner
Dec 10, 1999·The Journal of Clinical Investigation·F Liang, D G Gardner
Jun 24, 2010·Endocrine Journal·Koichiro Kuwahara, Kazuwa Nakao
Jan 8, 2010·Drug Design, Development and Therapy·Brian Casserly, James R Klinger
Feb 22, 2008·The American Journal of Cardiology·Abelardo Martinez-RumayorJames L Januzzi
Apr 20, 2005·Regulatory Peptides·Kenneth K MaAdolfo J de Bold
May 25, 2005·Peptides·Margot C LaPointe
Feb 8, 2011·Journal of cardiology·Toshio NishikimiKazuwa Nakao
Jul 13, 2012·Journal of Pharmacological Sciences·Koichiro KuwaharaKazuwa Nakao
Jan 1, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Mariela Mendez, Margot C LaPointe
Jan 24, 2006·American Journal of Physiology. Heart and Circulatory Physiology·Jian-Yong QianMargot C LaPointe
Mar 30, 2010·American Journal of Physiology. Heart and Circulatory Physiology·Quan He
Apr 15, 2000·The Journal of Biological Chemistry·F LiangD G Gardner
Nov 5, 1997·The Journal of Biological Chemistry·F LiangD G Gardner
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Sep 18, 2002·American Journal of Physiology. Heart and Circulatory Physiology·Margot C LaPointeQuan He

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