Shirokova, Natalia; Kang, Chifei; Fernandez Tenorio, Miguel; Wang, Wei; Wang, Qiongling; Wehrens, Xander H.T.; Niggli, Ernst (2014). RETRACTED: Oxidative Stress and Ca2+ Release Events in Mouse Cardiomyocytes. Biophysical journal, 107(12), pp. 2815-2827. Biophysical Society 10.1016/j.bpj.2014.10.054
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Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca2+ signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca2+ release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxidation of RyR2s was found to increase the open probability of the channel, whereas CaMKII can be activated independent of Ca2+ through oxidation. Here, we investigated how oxidative stress affects RyR2 function and SR Ca2+ signaling in situ, by analyzing Ca2+ sparks in permeabilized mouse cardiomyocytes under a broad range of oxidative conditions. The results show that with increasing oxidative stress Ca2+ spark duration is prolonged. In addition, long and very long-lasting (up to hundreds of milliseconds) localized Ca2+ release events started to appear, eventually leading to sarcoplasmic reticulum (SR) Ca2+ depletion. These changes of release duration could be prevented by the CaMKII inhibitor KN93 and did not occur in mice lacking the CaMKII-specific S2814 phosphorylation site on RyR2. The appearance of long-lasting Ca2+ release events was paralleled by an increase of RyR2 oxidation, but also by RyR-S2814 phosphorylation, and by CaMKII oxidation. Our results suggest that in a strongly oxidative environment oxidation-dependent activation of CaMKII leads to RyR2 phosphorylation and thereby contributes to the massive prolongation of SR Ca2+ release events.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Physiology |
UniBE Contributor: |
Fernandez Tenorio, Miguel, Niggli, Ernst |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
0006-3495 |
Publisher: |
Biophysical Society |
Language: |
English |
Submitter: |
Stefan von Känel-Zimmermann |
Date Deposited: |
29 Jan 2015 12:21 |
Last Modified: |
05 Dec 2022 14:39 |
Publisher DOI: |
10.1016/j.bpj.2014.10.054 |
Additional Information: |
Retraction Note: After the publication of this paper, the authors became aware that data reported in several figures (Figs. 1, 2A, 3A, 4, and 5B) had been incorrectly analyzed and annotated. Some details about the solution protocol were also missing from the Materials and Methods section. These mistakes were unintentional. It is the authors’ judgment that the mistakes are too extensive to allow for a published correction. Therefore, all the authors have agreed to retract this paper. |
BORIS DOI: |
10.7892/boris.62066 |
URI: |
https://boris.unibe.ch/id/eprint/62066 |
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