+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Oxidative stress and ca(2+) release events in mouse cardiomyocytes

Oxidative stress and ca(2+) release events in mouse cardiomyocytes

Biophysical Journal 107(12): 2815-2827

Cellular oxidative stress, associated with a variety of common cardiac diseases, is well recognized to affect the function of several key proteins involved in Ca(2+) signaling and excitation-contraction coupling, which are known to be exquisitely sensitive to reactive oxygen species. These include the Ca(2+) release channels of the sarcoplasmic reticulum (ryanodine receptors or RyR2s) and the Ca(2+)/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 Ca(2+) through oxidation. Here, we investigated how oxidative stress affects RyR2 function and SR Ca(2+) signaling in situ, by analyzing Ca(2+) sparks in permeabilized mouse cardiomyocytes under a broad range of oxidative conditions. The results show that with increasing oxidative stress Ca(2+) spark duration is prolonged. In addition, long and very long-lasting (up to hundreds of milliseconds) localized Ca(2+) release events started to appear, eventually leading to sarcoplasmic reticulum (SR) Ca(2+) 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 Ca(2+) 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 Ca(2+) release events.

(PDF emailed within 0-6 h: $19.90)

Accession: 058488894

Download citation: RISBibTeXText

PMID: 25517148

DOI: 10.1016/j.bpj.2014.10.054

Related references

Female adult mouse cardiomyocytes are protected against oxidative stress. Hypertension 55(5): 1172-1178, 2010

Recovery of oxidative stress-induced damage in Cisd2-deficient cardiomyocytes by sustained release of ferulic acid from injectable hydrogel. Biomaterials 103: 207-218, 2016

Exogenous taurine attenuates mitochondrial oxidative stress and endoplasmic reticulum stress in rat cardiomyocytes. Acta Biochimica et Biophysica Sinica 45(5): 359-367, 2013

Putative role of intracellular Zn(2+) release during oxidative stress: a trigger to restore cellular thiol content that is decreased by oxidative stress. Journal of Physiological Sciences 61(5): 403-409, 2012

Thymosin beta 4 protects cardiomyocytes from oxidative stress by targeting anti-oxidative enzymes and anti-apoptotic genes. Plos One 7(8): E42586-E42586, 2013

Neurobehavioral impairments, generation of oxidative stress and release of pro-apoptotic factors after chronic exposure to sulphur mustard in mouse brain. Toxicology and Applied Pharmacology 240(2): 208-218, 2009

2,3-Butanedione monoxime does not protect cardiomyocytes under oxidative stress. Cell Biochemistry and Function 24(5): 413-418, 2005

NF-κB mediated miR-21 regulation in cardiomyocytes apoptosis under oxidative stress. Free Radical Research 48(3): 282-291, 2014

Oxidative stress enhances phosphorylation of p53 in neonatal rat cardiomyocytes. Molecular and Cellular Biochemistry 303(1-2): 167-174, 2007

Both hydroxylamine and nitroxide protect cardiomyocytes from oxidative stress. Free Radical Biology & Medicine. 24(1): 66-75,. 1, 1998

β-Hydroxybutyrate elevation as a compensatory response against oxidative stress in cardiomyocytes. Biochemical and Biophysical Research Communications 475(4): 322-328, 2016

SIRT5: a safeguard against oxidative stress-induced apoptosis in cardiomyocytes. Cellular Physiology and Biochemistry 32(4): 1050-1059, 2014

Oleic acid mitigates TNF-α-induced oxidative stress in rat cardiomyocytes. Molecular and Cellular Biochemistry 372(1-2): 75-82, 2013

Isoproterenol-induced oxidative stress in freshly isolated rat cardiomyocytes. Toxicology Letters (Shannon) 116(Suppl 1): 79, September 1st, 2000

Adiponectin modulates oxidative stress-induced autophagy in cardiomyocytes. Plos One 8(7): E68697-E68697, 2014