کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1909563 1046730 2010 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Redox-mediated reciprocal regulation of SERCA and Na+–Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی سالمندی
پیش نمایش صفحه اول مقاله
Redox-mediated reciprocal regulation of SERCA and Na+–Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes
چکیده انگلیسی

Myocardial failure is associated with increased oxidative stress and abnormal excitation–contraction coupling characterized by depletion of sarcoplasmic reticulum (SR) Ca2+ stores and a reduction in Ca2+-transient amplitude. Little is known about the mechanisms whereby oxidative stress affects Ca2+ 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 Ca2+ depletion via redox-mediated regulation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) and the sodium–Ca2+ exchanger (NCX) and that this is associated with thiol oxidation. Adult rat ventricular myocytes paced at 5 Hz were superfused with H2O2 (100 μM, 15 min). H2O2 caused a progressive decrease in cell shortening followed by diastolic arrest, which was associated with decreases in SR Ca2+ content, systolic [Ca2+]i, and Ca2+-transient amplitude, but no change in diastolic [Ca2+]i. H2O2 caused reciprocal effects on the activities of SERCA (decreased) and NCX (increased). Pretreatment with the NCX inhibitor KB-R7943 before H2O2 increased diastolic [Ca2+]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 Ca2+ depletion involves reciprocal regulation of SERCA and NCX, possibly via direct oxidative modification of both proteins.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Free Radical Biology and Medicine - Volume 48, Issue 9, 1 May 2010, Pages 1182–1187
نویسندگان
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