Aldosterone directly induces myocyte apoptosis through calcineurin-dependent pathways

Circulation
Akiko ManoHiroaki Matsubara

Abstract

Aldosterone has recently attracted considerable attention for its involvement in the pathophysiology of heart failure, in which apoptotic cell loss plays a critical role. This study examined whether aldosterone directly induces myocyte apoptosis via its specific receptors. Neonatal rat cardiac myocytes were exposed to aldosterone (10(-8) to 10(-5) mol/L). Nuclear staining with Hoechst 33258 showed that aldosterone induced myocyte apoptosis in a dose- and time-dependent fashion. Treatment of myocytes with 10(-5) mol/L aldosterone significantly increased the percentage of apoptosis (15.5+/-1.4%) compared with serum-deprived control (7.3+/-0.6%). Radio ligand binding assay revealed the existence of plasma membrane receptor with high affinity (K(d), 0.2 nmol/L) for aldosterone in cardiac myocytes but not in fibroblasts. Aldosterone rapidly (approximately 30 seconds) mobilized [Ca2+]i that was blocked by neomycin. Aldosterone induced dephosphorylation of the proapoptotic protein Bad, enhancement of mitochondrial permeability transition, decrease in mitochondrial membrane potential, and release of cytochrome c from the mitochondria into the cytosol with concomitant activation of caspase-3. These effects of aldosterone were inhibited ...Continue Reading

References

Oct 21, 1994·Cell·Z N Oltvai, S J Korsmeyer
Jun 1, 1993·American Journal of Hypertension·S E CampbellK T Weber
Oct 17, 1996·The New England Journal of Medicine·J NarulaB A Khaw
Mar 28, 1998·The Journal of Biological Chemistry·J S SilvestreC Delcayre
Jan 23, 1999·BioFactors·V PetronilliF Di Lisa
Jun 18, 1999·Journal of Molecular and Cellular Cardiology·S H SlightK T Weber
Nov 18, 2000·Circulation·E Braunwald, M R Bristow
Sep 15, 2001·American Journal of Physiology. Heart and Circulatory Physiology·J ShiraishiM Nakagawa
Nov 13, 2002·Journal of the American College of Cardiology·Michel F RousseauUNKNOWN Belgian RALES Investigators
Mar 12, 2003·Journal of the American College of Cardiology·Satoshi YamanakaMasao Nakagawa
Apr 2, 2003·The New England Journal of Medicine·Bertram PittUNKNOWN Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study Investigators

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Citations

Jan 13, 2012·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Wei HuMei-Ying Lin
Aug 3, 2010·Cardiovascular Drugs and Therapy·Felipe A Martinez
Dec 15, 2007·Heart Failure Reviews·Hiroyuki Yaoita, Yukio Maruyama
Nov 28, 2013·Pharmacology & Therapeutics·T N A van den BergNiels P Riksen
May 24, 2005·Journal of Molecular and Cellular Cardiology·Jatin G BurnistonDavid F Goldspink
Feb 22, 2008·Proceedings of the National Academy of Sciences of the United States of America·Matilde ColellaTullio Pozzan
Apr 23, 2010·Clinical and Experimental Pharmacology & Physiology·Gavin P Vinson, John P Coghlan
Apr 28, 2009·American Journal of Physiology. Heart and Circulatory Physiology·Deepa S De SilvaFlora Sam
May 9, 2008·American Journal of Physiology. Renal Physiology·Jayant T MathewPravin C Singhal
Feb 9, 2012·Physiology·Haipeng Sun, Yibin Wang
Jul 11, 2009·Nephron. Experimental Nephrology·Cheng ChenGuohua Ding
Jun 18, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Shinsuke SuzukiMasunori Matsuzaki
Jun 26, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Mitsuo TakedaHiroaki Matsubara
Mar 25, 2008·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hironori HayashiHiroaki Matsubara
Jul 1, 2009·Journal of Endocrinological Investigation·F GalettaG Santoro
Dec 24, 2009·Canadian Journal of Physiology and Pharmacology·Katherine V WestcottFrans H H Leenen
Feb 6, 2008·Expert Review of Cardiovascular Therapy·Renee Margossian
Nov 3, 2009·Steroids·Claudia GrossmannMichael Gekle
Jul 19, 2014·Journal of Cardiovascular Medicine·Giuseppe VergaroRosanna Abbate
Jan 27, 2009·International Journal of Cardiology·G P VyssoulisC I Stefanadis
Sep 3, 2010·Journal of Korean Medical Science·Hyung Joo SohnJoo Won Lee
Oct 18, 2008·American Journal of Hypertension·Gus Q ZhangWeiguo Zhang
Dec 5, 2006·Hearing Research·Colleen G Le PrellJosef M Miller
Mar 4, 2014·Asian Cardiovascular & Thoracic Annals·Jusuf RachmatGunanti Soejono
Aug 3, 2007·American Journal of Physiology. Renal Physiology·Hitesh PatniPravin C Singhal
May 27, 2011·Equine Veterinary Journal. Supplement·A JanssonC Kvart
Apr 10, 2015·Journal of Cellular Physiology·Stephanie KönemannStephan B Felix

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