Intracellular Zinc Modulates Cardiac Ryanodine Receptor-mediated Calcium Release

Woodier, Jason; Rainbow, Richard D.; Stewart, Alan J.; Pitt, Samantha J.

doi:10.1074/jbc.m115.661280

Cited by 70 publications

(74 citation statements)

References 50 publications

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“…Therefore, our study suggests that zinc administration attenuated infarct-induced ventricular remodeling, associated with improved systolic and diastolic function. Interesting, zinc improved some functional variables even in normal rats, similar to the finding of a previous study [8], probably due to a combination of competitive inhibition of calcium influx through the l-type calcium channel, and the modulation of ryanodine receptor-mediated calcium release [8,10].…”

Section: Discussionsupporting

confidence: 83%

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Gonçalves¹,

Polegato²,

Fernandes³

et al. 2018

Cell Physiol Biochem

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Background/Aims: The objective of our study was to evaluate the effects of zinc supplementation on cardiac remodeling following acute myocardial infarction in rats. Methods: Animals were subdivided into 4 groups and observed for 3 months: 1) Sham Control; 2) Sham Zinc: Sham animals receiving zinc supplementation; 3) Infarction Control; 4) Infarction Zinc. After the followup period, we studied hypertrophy and ventricular geometry, functional alterations in vivo and in vitro, changes related to collagen, oxidative stress, and inflammation, assessed by echocardiogram, isolated heart study, western blot, flow cytometer, morphometry, and spectrophotometry. Results: Infarction induced a significant worsening of the functional variables. On the other hand, zinc attenuated both systolic and diastolic cardiac dysfunction induced by infarction. Considering the infarct size, there was no difference between the groups. Catalase and superoxide dismutase decreased in infarcted animals, and zinc increased its activity. We found higher expression of collagens I and III in infarcted animals, but there was no effect of zinc supplementation. Likewise, infarcted animals had higher levels of IL-10, but without zinc interference. Nrf-2 values were not different among the groups. Infarction increased the amount of Treg cells in the spleen as well as the amount of total lymphocytes. Zinc increased the amount of CD4+ in infarcted animals, but we did not observe effects in relation to Treg cells. Conclusion: zinc attenuates cardiac remodeling after infarction in rats; this effect is associated with modulation of antioxidant enzymes, but without the involvement of collagens I and III, Nrf-2, IL-10, and Treg cells.

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Section: Discussionsupporting

confidence: 83%

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Gonçalves¹,

Polegato²,

Fernandes³

et al. 2018

Cell Physiol Biochem

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“…DTDP induces Zn 2+ liberation from intracellular stores (Aizenman et al, 2000), which, in turn can mediate Ca 2+ release via ryanodine receptors (Woodier et al, 2015; Schulien et al, 2016). As such, Zn 2+ , under certain circumstances, may induce calcineurin-dependent K V 2.1 declustering (Schulien et al, 2016).…”

Section: Resultsmentioning

confidence: 99%

Disruption of K V 2.1 somato-dendritic clusters prevents the apoptogenic increase of potassium currents

Justice

Schulien

et al. 2017

Neuroscience

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As the predominant mediator of the delayed rectifier current, KV2.1 is an important regulator of neuronal excitability. KV2.1, however, also plays a well-established role in apoptotic cell death. Apoptogenic stimuli induce syntaxin-dependent trafficking of KV2.1, resulting in an augmented delayed rectifier current that acts as a conduit for K+ efflux required for pro-apoptotic protease/nuclease activation. Recent evidence suggests that KV2.1 somato-dendritic clusters regulate the formation of endoplasmic reticulum–plasma membrane junctions that function as scaffolding sites for plasma membrane trafficking of ion channels, including KV2.1. However, it is unknown whether KV2.1 somato-dendritic clusters are required for apoptogenic trafficking of KV2.1. By overexpression of a protein derived from the C-terminus of the cognate channel KV2.2 (KV2.2CT), we induced calcineurin-independent disruption of KV2.1 somato-dendritic clusters in rat cortical neurons, without altering the electrophysiological properties of the channel. We observed that KV2.2CT-expressing neurons are less susceptible to oxidative stress-induced cell death. Critically, expression of KV2.2CT effectively blocked the increased current density of the delayed rectifier current associated with oxidative injury, supporting a vital role of KV2.1-somato-dendritic clusters in apoptogenic increases in KV2.1-mediated currents.

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“…Various studies suggest that defective Zn 2+ handling contributes to cardiomyopathies including altered contractility and heart failure [89,[108][109][110]. Indeed, it has been hypothesised that increased cytosolic Zn 2+ can influence cardiac excitationcontraction coupling through regulation of the ryanodine receptor in cardiomyocytes [111,112]. The combined effects of Zn 2+ and Ca 2+ dyshomeostasis are also thought to generate oxidative stress, lead to cardiac myocyte necrosis and replacement fibrosis [113].…”

Section: +mentioning

confidence: 99%

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

Blindauer

Khazaipoul²,

Yu³

et al. 2016

CTMC

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(2016) Fatty acid-mediated inhibition of metal binding to the multi-metal site on serum albumin : implications for cardiovascular disease. Current Trends in Medicinal Chemistry, 16. Permanent WRAP URL:http://wrap.warwick.ac.uk/78963 Copyright and reuse:The Warwick Research Archive Portal (WRAP) makes this work by researchers of the University of Warwick available open access under the following conditions. Copyright © and all moral rights to the version of the paper presented here belong to the individual author(s) and/or other copyright owners. To the extent reasonable and practicable the material made available in WRAP has been checked for eligibility before being made available.Copies of full items can be used for personal research or study, educational, or not-for-profit purposes without prior permission or charge. Provided that the authors, title and full bibliographic details are credited, a hyperlink and/or URL is given for the original metadata page and the content is not changed in any way.Publisher's statement: © Bentham Science Publishers. http://dx.doi.org/10.2174/1568026616666160216155927 A note on versions:The version presented here may differ from the published version or, version of record, if you wish to cite this item you are advised to consult the publisher's version. Please see the 'permanent WRAP URL' above for details on accessing the published version and note that access may require a subscription. Abstract: Human serum albumin (HSA) is the major protein in blood plasma and is responsible for circulatory transport of a range of small molecules including fatty acids, metal ions and drugs. We previously identified the major plasma Zn 2+ transport site on HSA and revealed that fatty-acid binding (at a distinct site called the FA2 site) and Zn 2+ binding are interdependent via an allosteric mechanism. Since binding affinities of long-chain fatty acids exceed those of plasma Zn 2+ , this means that under certain circumstances the binding of fatty acid molecules to HSA is likely to diminish HSA Zn 2+ -binding, and hence affects the control of circulatory and cellular Zn 2+ dynamics. This relationship between circulatory fatty acid and Zn 2+ dynamics is likely to have important physiological and pathological implications, especially since it has been recognised that Zn 2+ acts as a signalling agent in many cell types. Fatty acid levels in the blood are dynamic, but most importantly, chronic elevation of plasma fatty acid levels is associated with some metabolic disorders and disease states -including myocardial infarction and other cardiovascular diseases. In this article, we briefly review the metalbinding properties of albumin and highlight the importance of their interplay with fatty acid binding. We also consider the impact of this dynamic link upon levels and speciation of plasma Zn 2+ , its effect upon cellular Zn 2+ homeostasis and its relevance to cardiovascular and circulatory processes in health and disease.

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Intracellular Zinc Modulates Cardiac Ryanodine Receptor-mediated Calcium Release

Cited by 70 publications

References 50 publications

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Zinc Supplementation Attenuates Cardiac Remodeling After Experimental Myocardial Infarction

Disruption of K V 2.1 somato-dendritic clusters prevents the apoptogenic increase of potassium currents

Fatty Acid-Mediated Inhibition of Metal Binding to the Multi-Metal Site on Serum Albumin: Implications for Cardiovascular Disease

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