Redox-mediated reciprocal regulation of SERCA and Na+–Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes

Kuster, Gabriela M.; Lancel, Steve; Zhang, Jingmei; Communal, Catherine; Trucillo, Mario P.; Lim, Chee Chew; Pfister, Otmar; Weinberg, Ellen O.; Cohen, Richard A.; Liao, Ronglih

doi:10.1016/j.freeradbiomed.2010.01.038

Cited by 118 publications

(95 citation statements)

References 29 publications

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“…In addition, ROS induced decreased cytosolic Ca + 2 associated with decreased activity of L-type Ca 2 + channels (100) and RyRs (287), or increased activity of NCX (219) has also been shown in other studies, and this may cause shortening of the action potential followed by loss of excitability as shown by Jabr and Cole (126). The contradictory results on ROS effects on ion channels and the action potential might be due to species differences (44,276) in the concentration (89) and the type of ROS involved (41) and the number and type of channels affected (12,149). In support of this idea, Tokube et al (250) reported ROS-induced biphasic changes in the action potential duration, with initial lengthening of the action potential due to a rapid decrease in whole-cell I K and subsequent shortening due to a decrease of whole-cell I Ca and increase in ATP-sensitive outward K + current (I KATP ).…”

Section: Overview Of Ros Effects On Cardiac Ion Currents Actionmentioning

confidence: 82%

“…Indeed, ROS-induced membrane depolarization occurred with increased Na + window current (the window current results from the overlap of activation and inactivation steady-state curves due to depolarized membrane voltages that are sufficient to transiently open a few available channels) (27), increased activity of NCX (90), inhibition of the inward I K (199), activation of an inwardly directed nonselective cationic current (182), increased intracellular Ca + 2 concentration associated with increased activity of the L-type Ca + 2 channels (117) or ryanodine receptors (RyRs) (9), and decreased activity of the sarcoplasmic reticulum (SR) Ca 2 + pump SERCA2a (149). An example from guinea pig myocytes (Fig.…”

Section: Overview Of Ros Effects On Cardiac Ion Currents Actionmentioning

confidence: 99%

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Redox Control of Cardiac Excitability

Aggarwal

Makielski

2013

Antioxidants & Redox Signaling

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Reactive oxygen species (ROS) have been associated with various human diseases, and considerable attention has been paid to investigate their physiological effects. Various ROS are synthesized in the mitochondria and accumulate in the cytoplasm if the cellular antioxidant defense mechanism fails. The critical balance of this ROS synthesis and antioxidant defense systems is termed the redox system of the cell. Various cardiovascular diseases have also been affected by redox to different degrees. ROS have been indicated as both detrimental and protective, via different cellular pathways, for cardiac myocyte functions, electrophysiology, and pharmacology. Mostly, the ROS functions depend on the type and amount of ROS synthesized. While the literature clearly indicates ROS effects on cardiac contractility, their effects on cardiac excitability are relatively under appreciated. Cardiac excitability depends on the functions of various cardiac sarcolemal or mitochondrial ion channels carrying various depolarizing or repolarizing currents that also maintain cellular ionic homeostasis. ROS alter the functions of these ion channels to various degrees to determine excitability by affecting the cellular resting potential and the morphology of the cardiac action potential. Thus, redox balance regulates cardiac excitability, and under pathological regulation, may alter action potential propagation to cause arrhythmia. Understanding how redox affects cellular excitability may lead to potential prophylaxis or treatment for various arrhythmias. This review will focus on the studies of redox and cardiac excitation. Antioxid. Redox Signal. 18, 432-468.

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Section: Overview Of Ros Effects On Cardiac Ion Currents Actionmentioning

confidence: 82%

Section: Overview Of Ros Effects On Cardiac Ion Currents Actionmentioning

confidence: 99%

Redox Control of Cardiac Excitability

Aggarwal

Makielski

2013

Antioxidants & Redox Signaling

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“…To see this illustration in color, the reader is referred to the web version of this article at www.liebertpub.com/ars (125). Consistent with this increase in activity with HF, ROS has also been shown to increase NCX activity via oxidation (59,100,130). However, there is a negative consequence of this increased NCX activity, which is to increase the propensity to generate arrhythmias (7).…”

Section: Sr Ca 2 + -Atpasementioning

confidence: 76%

“…With the enhanced b-AR drive and increased epi/norepi in HF, MAO activity and expression (both MAO A and B) are increased resulting in enhanced H 2 O 2 levels (86,87). In addition, under certain conditions (as occurs in HF), NO production via NOS is interrupted resulting in the production of O 2 -, termed NOS uncoupling (154 (60,61,64,67,100,109,121). These effects of ROS on myocyte Ca 2 + handling are similar to what is observed in failing myocytes.…”

Section: Redox Signalingmentioning

confidence: 99%

Abnormal Ca²⁺Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance

Ziolo

Houser

2014

Antioxidants & Redox Signaling

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Significance: Heart failure (HF) results from poor heart function and is the leading cause of death in Western society. Abnormalities of Ca 2+ handling at the level of the ventricular myocyte are largely responsible for much of the poor heart function. Recent Advances: Although studies have unraveled numerous mechanisms for the abnormal Ca 2+ handling, investigations over the past decade have indicated that much of the contractile dysfunction and adverse remodeling that occurs in HF involves oxidative stress. Critical Issues: Regrettably, antioxidant therapy has been an immense disappointment in clinical trials. Thus, redox signaling is being reassessed to elucidate why antioxidants failed to treat HF. Future Directions: A recently identified aspect of redox signaling (specifically the superoxide anion radical) is its interaction with nitric oxide, known as the nitroso-redox balance. There is a large nitroso-redox imbalance with HF, and we suggest that correcting this imbalance may be able to restore myocyte contraction and improve heart function.

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“…Lactate production or removal controlled by lactate dehydrogenase (LDH), affects the NAD ϩ /NADH ratio, which in turn affects GSH/GSSG status. Altered GSH/GSSG will affect the critical thiol regulatory proteins (214), including sarcoendoplasmic reticulum Ca ϩϩ ATPase (SERCA) (60,116), and transcription factors such as CREB, known to have two activity-determining thiols (79), causing changes in gene transcription. Changes in SERCA activity will affect calcium homeostasis that in turn will affect gene expression through the calcineurin-nuclear factor of activated T cells (NFAT) pathway (43).…”

Section: The Dynamic Range Of Lactate Signaling In Activation Of Thementioning

confidence: 99%

Exercise tames the wild side of the Myc network: a hypothesis

Gohil

Brooks

2012

American Journal of Physiology-Endocrinology and Metabolism

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Gohil K, Brooks GA. Exercise tames the wild side of the Myc network: a hypothesis. Am J Physiol Endocrinol Metab 303: E18 -E30, 2012. First published April 24, 2012; doi:10.1152/ajpendo.00027.2012We propose that the welldocumented therapeutic actions of repeated physical activities over human lifespan are mediated by the rapidly turning over proto-oncogenic Myc (myelocytomatosis) network of transcription factors. This transcription factor network is unique in utilizing promoter and epigenomic (acetylation/deacetylation, methylation/demethylation) mechanisms for controlling genes that include those encoding intermediary metabolism (the primary source of acetyl groups), mitochondrial functions and biogenesis, and coupling their expression with regulation of cell growth and proliferation. We further propose that remote functioning of the network occurs because there are two arms of this network, which consists of driver cells (e.g., working myocytes) that metabolize carbohydrates, fats, proteins, and oxygen and produce redox-modulating metabolites such as H 2O2, NAD ϩ , and lactate. The exercise-induced products represent autocrine, paracrine, or endocrine signals for target recipient cells (e.g., aortic endothelium, hepatocytes, and pancreatic ␤-cells) in which the metabolic signals are coupled with genomic networks and interorgan signaling is activated. And finally, we propose that lactate, the major metabolite released from working muscles and transported into recipient cells, links the two arms of the signaling pathway. Recently discovered contributions of the Myc network in stem cell development and maintenance further suggest that regular physical activity may prevent age-related diseases such as cardiovascular pathologies, cancers, diabetes, and neurological functions through prevention of stem cell dysfunctions and depletion with aging. Hence, regular physical activities may attenuate the various deleterious effects of the Myc network on health, the wild side of the Myc-network, through modulating transcription of genes associated with glucose and energy metabolism and maintain a healthy human status. myelocytomatosis; lactate shuttle; glycolysis; mitochondrial reticulum; mitochondrial biogenesis; mitochondrial dynamics; exertion; health; chronic diseases REGULAR PHYSICAL ACTIVITIES ameliorate or prevent numerous pathologies frequently associated with aging that include cardiovascular dysfunctions (103,183,200), diabetes (2,17,178,201,214), dementias (41), depression (86,195), and cancers (42, 165). Importantly, physical activity protects against some of these pathologies in a dose-dependent relationship (114,123,222), possibly through targeting the endothelium (173,208,212) that displays tissue-specific phenotypes (125,158,175,191). The molecular basis of this dose-dependent, regular, and "remote action" of skeletal muscle activity on functionally distinct organs needs clarification. In skeletal muscles, the initial and driving organ, transcriptional processes are activated by the exercise stimulus, which ...

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Redox-mediated reciprocal regulation of SERCA and Na+–Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes

Cited by 118 publications

References 29 publications

Redox Control of Cardiac Excitability

Redox Control of Cardiac Excitability

Abnormal Ca²⁺Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance

Exercise tames the wild side of the Myc network: a hypothesis

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Redox-mediated reciprocal regulation of SERCA and Na+–Ca2+ exchanger contributes to sarcoplasmic reticulum Ca2+ depletion in cardiac myocytes

Cited by 118 publications

References 29 publications

Redox Control of Cardiac Excitability

Redox Control of Cardiac Excitability

Abnormal Ca2+Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance

Exercise tames the wild side of the Myc network: a hypothesis

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Abnormal Ca²⁺Cycling in Failing Ventricular Myocytes: Role of NOS1-Mediated Nitroso-Redox Balance