Adenylyl cyclase type VI gene transfer reduces phospholamban expression in cardiac myocytes via activating transcription factor 3.

The Journal of Biological Chemistry
Mei Hua GaoH Kirk Hammond

Abstract

Cardiac-directed expression of adenylyl cyclase type VI (AC(VI)) increases stimulated cAMP production, improves heart function, and increases survival in cardiomyopathy. In contrast, pharmacological agents that increase intracellular levels of cAMP have detrimental effects on cardiac function and survival. We wondered whether effects that are independent of cAMP might be responsible for these salutary outcomes associated with AC(VI) expression. We therefore conducted a series of experiments focused on how gene transcription is influenced by AC(VI) in cultured neonatal rat cardiac myocytes, with a particular focus on genes that might influence cardiac function. We found that overexpression of AC(VI) down-regulated mRNA and protein expression of phospholamban, an inhibitor of the sarcoplasmic reticulum Ca(2+)-ATPase. We determined that the cAMP-responsive-like element in the phospholamban (PLB) promoter was critical for down-regulation by AC(VI). Overexpression of AC(VI) did not alter the expression of CREB, CREM, ATF1, ATF2, or ATF4 proteins. In contrast, overexpression of AC(VI) increased expression of ATF3 protein, a suppressor of transcription. Following AC(VI) gene transfer, when cardiac myocytes were stimulated with isoprot...Continue Reading

References

Oct 30, 1992·Biochemical and Biophysical Research Communications·D C Johns, A M Feldman
Aug 25, 1990·Lancet·R Lim
Aug 25, 1990·Lancet·H Ikram, I G Crozier
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·M GaoH K Hammond
Sep 16, 1998·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·F U MüllerW Schmitz
Apr 13, 1999·Journal of Molecular and Cellular Cardiology·C F McTiernanA M Feldman
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·G W DornS B Liggett
Jan 21, 2000·Journal of Molecular and Cellular Cardiology·C F McTiernanA M Feldman
Apr 5, 2000·The Journal of Biological Chemistry·C D WolfgangT Hai
Dec 13, 2000·Journal of Molecular and Cellular Cardiology·A G Brittsan, E G Kranias
Sep 21, 2001·Molecular and Cellular Biology·A S WeinmannP J Farnham
Feb 28, 2002·Circulation·Federica del MonteRoger J Hajjar
May 9, 2002·Circulation·David M RothH Kirk Hammond
Oct 24, 2002·Journal of Molecular and Cellular Cardiology·Kiyoshi NoboriMitsuaki Isobe
Apr 23, 2003·Biochemical and Biophysical Research Communications·Susumu MinamisawaRumiko Matsuoka
Oct 7, 2003·Proceedings of the National Academy of Sciences of the United States of America·Rebecca MartoneMichael Snyder
Dec 12, 2003·Brain Research. Molecular Brain Research·Andree G PearsonMichael Dragunow
Jun 17, 2004·Molecular and Cellular Biology·Matthew G HartmanTsonwin Hai

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Citations

Apr 27, 2012·Gene Therapy·T TangH Kirk Hammond
Oct 8, 2008·The Journal of Biological Chemistry·Mei Hua GaoH Kirk Hammond
Oct 23, 2013·PloS One·Mei Hua GaoH Kirk Hammond
Mar 1, 2011·Journal of Molecular and Cellular Cardiology·Mei Hua Gao, H Kirk Hammond
Jan 5, 2011·Biochemical and Biophysical Research Communications·Yasuo SuganoH Kirk Hammond
Dec 1, 2008·Clinical and Translational Science·Natalia PetrashevskayaStephen B Liggett
Nov 30, 2006·Annals of the New York Academy of Sciences·H Kirk Hammond
Mar 11, 2006·European Journal of Pharmacology·Michael A Beazely, Val J Watts
Sep 30, 2006·Biochimica Et Biophysica Acta·Petter Kirkeby RisøeMaria K Dahle
May 10, 2019·Journal of the American Heart Association·Jake M KiesermanArthur M Feldman
Mar 23, 2017·Human Gene Therapy·William F Penny, H Kirk Hammond
Oct 6, 2020·Frontiers in Physiology·Alexandra NjegicElizabeth J Cartwright

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