Chapter title |
Functional Impact of Ryanodine Receptor Oxidation on Intracellular Calcium Regulation in the Heart
|
---|---|
Chapter number | 2 |
Book title |
Reviews of Physiology, Biochemistry and Pharmacology, Vol. 171
|
Published in |
Reviews of Physiology, Biochemistry and Pharmacology, June 2016
|
DOI | 10.1007/112_2016_2 |
Pubmed ID | |
Book ISBNs |
978-3-31-943813-9, 978-3-31-943814-6
|
Authors |
Aleksey V. Zima, Stefan R. Mazurek |
Editors |
Bernd Nilius, Pieter de Tombe, Thomas Gudermann, Reinhard Jahn, Roland Lill, Ole H. Petersen |
Abstract |
Type 2 ryanodine receptor (RyR2) serves as the major intracellular Ca(2+) release channel that drives heart contraction. RyR2 is activated by cytosolic Ca(2+) via the process of Ca(2+)-induced Ca(2+) release (CICR). To ensure stability of Ca(2+) dynamics, the self-reinforcing CICR must be tightly controlled. Defects in this control cause sarcoplasmic reticulum (SR) Ca(2+) mishandling, which manifests in a variety of cardiac pathologies that include myocardial infarction and heart failure. These pathologies are also associated with oxidative stress. Given that RyR2 contains a large number of cysteine residues, it is no surprise that RyR2 plays a key role in the cellular response to oxidative stress. RyR's many cysteine residues pose an experimental limitation in defining a specific target or mechanism of action for oxidative stress. As a result, the current understanding of redox-mediated RyR2 dysfunction remains incomplete. Several oxidative modifications, including S-glutathionylation and S-nitrosylation, have been suggested playing an important role in the regulation of RyR2 activity. Moreover, oxidative stress can increase RyR2 activity by forming disulfide bonds between two neighboring subunits (intersubunit cross-linking). Since intersubunit interactions within the RyR2 homotetramer complex dictate the channel gating, such posttranslational modification of RyR2 would have a significant impact on RyR2 function and Ca(2+) regulation. This review summarizes recent findings on oxidative modifications of RyR2 and discusses contributions of these RyR2 modifications to SR Ca(2+) mishandling during cardiac pathologies. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 36 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 12 | 33% |
Student > Master | 5 | 14% |
Professor > Associate Professor | 3 | 8% |
Other | 2 | 6% |
Student > Bachelor | 2 | 6% |
Other | 3 | 8% |
Unknown | 9 | 25% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 7 | 19% |
Medicine and Dentistry | 6 | 17% |
Agricultural and Biological Sciences | 4 | 11% |
Neuroscience | 2 | 6% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 3% |
Other | 4 | 11% |
Unknown | 12 | 33% |