Redox-mediated reciprocal regulation of SERCA and Na+-Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes

Kuster, Gabriela M. and Lancel, Steve and Zhang, Jingmei and Communal, Catherine and Trucillo, Mario P. and Lim, Chee C. and Pfister, Otmar and Weinberg, Ellen O. and Cohen, Richard A. and Liao, Ronglih and Siwik, Deborah A. and Colucci, Wilson S.. (2010) Redox-mediated reciprocal regulation of SERCA and Na+-Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes. Free radical biology & medicine, Vol. 48, H. 9. pp. 1182-1187.

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Official URL: http://edoc.unibas.ch/dok/A6006811

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Myocardial failure is associated with increased oxidative stress and abnormal excitation-contraction coupling characterized by depletion of sarcoplasmic reticulum (SR) Ca(2+) stores and a reduction in Ca(2+)-transient amplitude. Little is known about the mechanisms whereby oxidative stress affects Ca(2+) handling and contractile function; however, reactive thiols may be involved. We used an in vitro cardiomyocyte system to test the hypothesis that short-term oxidative stress induces SR Ca(2+) depletion via redox-mediated regulation of sarcoendoplasmic reticulum Ca(2+)-ATPase (SERCA) and the sodium-Ca(2+) exchanger (NCX) and that this is associated with thiol oxidation. Adult rat ventricular myocytes paced at 5 Hz were superfused with H(2)O(2) (100 microM, 15 min). H(2)O(2) caused a progressive decrease in cell shortening followed by diastolic arrest, which was associated with decreases in SR Ca(2+) content, systolic [Ca(2+)](i), and Ca(2+)-transient amplitude, but no change in diastolic [Ca(2+)](i). H(2)O(2) caused reciprocal effects on the activities of SERCA (decreased) and NCX (increased). Pretreatment with the NCX inhibitor KB-R7943 before H(2)O(2) increased diastolic [Ca(2+)](i) and mimicked the effect of SERCA inhibition with thapsigargin. These functional effects were associated with oxidative modification of thiols on both SERCA and NCX. In conclusion, redox-mediated SR Ca(2+) depletion involves reciprocal regulation of SERCA and NCX, possibly via direct oxidative modification of both proteins.
Faculties and Departments:03 Faculty of Medicine > Bereich Medizinische Fächer (Klinik) > Kardiologie
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Medizinische Fächer (Klinik) > Kardiologie
UniBasel Contributors:Pfister, Otmar
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Pergamon Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:24 May 2013 09:23
Deposited On:24 May 2013 09:14

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