Redox regulation of RyR-mediated Ca2+ release in muscle and neurons

Hidalgo, Cecilia; Bull, Ricardo; Behrens, María I.; Donoso, P

doi:10.4067/s0716-97602004000400007

Cited by 61 publications

(54 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…An RyR or IP 3 R channel is a homotetramer with each subunit containing many free cysteine residues that are susceptible to redox reaction by ROS. For instance, each of the four homologous 560 kDa RyR 1 proteins contains approximately 50 free cysteine residues [37] , and approximately 21 free cysteines per subunit of RyR 2 [38] . Changes in the redox state of RyR and IP 3 R would affect their activities.…”

Section: + Signalingmentioning

confidence: 99%

“…It is noteworthy that high concentration GSH (10 mmol/L) or DTT (2 mmol/L) itself strongly inhibits Ca 2+ release in cardiomyocytes [42] . In neurons, activation of RyR 3 by ROS might modify Ca 2+ -dependent long-term potentiation and long-term depression [37] . In the case of IP 3 R, it has been reported that O 2 · -enhances IP 3 -induced Ca 2+ release from fractionated vascular smooth muscle SR [43] , and oxidized GSH induces Ca 2+ release from IP 3 R in intact hepatocytes [44] .…”

Section: + Signalingmentioning

confidence: 99%

See 1 more Smart Citation

Cross-talk between calcium and reactive oxygen species signaling

Yuan

Wei

Zhang

et al. 2006

Acta Pharmacologica Sinica

219

167

View full text Add to dashboard Cite

Calcium (Ca 2+ ) and reactive oxygen species (ROS) constitute the most important intracellular signaling molecules participating in the regulation and integration of diverse cellular functions. Here we briefly review cross-talk between the two prominent signaling systems that finely tune the homeostasis and integrate functionality of Ca 2+ and ROS signaling systems can be both stimulatory and inhibitory, depending on the type of target proteins, the ROS species, the dose, duration of exposure, and the cell contexts. Such extensive and complex cross-talk might enhance signaling coordination and integration, whereas abnormalities in either system might propagate into the other system and undermine the stability of both systems.

show abstract

Section: + Signalingmentioning

confidence: 99%

Section: + Signalingmentioning

confidence: 99%

Cross-talk between calcium and reactive oxygen species signaling

Yuan

Wei

Zhang

et al. 2006

Acta Pharmacologica Sinica

219

167

View full text Add to dashboard Cite

show abstract

“…A sarcoplasmic reticulum (SR)-associated NAD(P)H oxidase coupled to superoxide anion radical production has been shown to modulate RyR-mediated Ca 2ϩ release in skeletal and cardiac muscle (33)(34)(35)(36). Oxidation-induced RyR activation is due to increased sensitivity of the channel to Ca 2ϩ activation as well as a decrease in Mg 2ϩ inhibition (24,25). Redox modulation of RyR channel activity may involve altered protein-protein interactions.…”

mentioning

confidence: 99%

“…In general, oxidizing reagents activate, whereas reducing reagents inhibit, channel activity (24,25). Pharmacological sulfydryl-reactive reagents, including thimerosal, dithiodipyridines, N-ethylmaleimide, and diamide, have been shown to activate skeletal and cardiac muscle RyRs (26 -28).…”

mentioning

confidence: 99%

Redox Sensitivity of the Ryanodine Receptor Interaction with FK506-binding Protein

Zissimopoulos

Docrat

Lai

2007

Journal of Biological Chemistry

View full text Add to dashboard Cite

The ryanodine receptor (RyR) calcium release channel functions as a redox sensor that is sensitive to channel modulators. The FK506-binding protein (FKBP) is an important regulator of channel activity, and disruption of the RyR2-FKBP12.6 association has been implicated in cardiac disease. In the present study, we investigated whether the RyR-FKBP association is redoxregulated. Using co-immunoprecipitation assays of solubilized native RyR2 from cardiac muscle sarcoplasmic reticulum ( and diamide differentially affected the RyR2-FKBP12.6 interaction, decreasing binding to ϳ75 and ϳ50% of control, respectively. In addition, the effect of H 2 O 2 was negligible when the channel was in its closed state or when applied after FKBP binding had occurred, whereas diamide was always effective. A cysteine-null mutant FKBP12.6 retained redox-sensitive interaction with RyR2, suggesting that the effect of the redox reagents is exclusively via sites on the ryanodine receptor. K201 (or JTV519), a drug that has been proposed to prevent FKBP12.6 dissociation from the RyR2 channel complex, did not restore normal FKBP binding under oxidizing conditions. Our results indicate that the redox state of the RyR is intimately connected with FKBP binding affinity. Ryanodine receptors (RyRs)2 are tetrameric intracellular Ca 2ϩ channels that mediate the release of Ca 2ϩ from the sarco/ endoplasmic reticulum in muscle and nonmuscle cells (1). Three genes coding for mammalian RyRs have been identified: RyR1 in skeletal muscle, RyR2 in heart and brain, and RyR3 in a number of tissues. The deduced primary structure of all RyRs suggests a hydrophobic C terminus forming the channel pore, with the remaining ϳ80% being cytoplasmic. RyR channel activity is regulated by Ca 2ϩ , Mg 2ϩ , ATP, phosphorylation and redox status, and a number of accessory proteins.The immunophilin, FK506-binding protein (FKBP), a receptor protein for the immunosuppressants, FK506 and rapamycin, is an essential component of the RyR-Ca 2ϩ release channel complex in both skeletal and cardiac muscle (2, 3). RyR1 binds to both FKBP12 and FKBP12.6 with similar affinities (4), whereas RyR2 associates specifically with the FKBP12.6 isoform (3, 5). The stoichiometry of the association is four molecules of FKBP per RyR tetrameric channel (i.e. one FKBP molecule for each RyR protomer) (3, 6). Mapping studies have failed to identify a unique FKBP-binding site, with evidence presented for three distinct RyR regions (N-terminal, central, and C-terminal domains) (7-12), suggesting that FKBP interaction may be stabilized by multiple physical contacts and/or may be conformation-sensitive. The functional effects of FKBP association with RyR have been suggested to include stabilization of the full conductance state (7,13,14), channel closure (5, 6, 15), and coupled gating between neighboring channels (16,17). These effects are highlighted in abnormal or disease states, where defective regulation of the RyR-FKBP association has been implicated in cardiomyopathy (18), cardiac hypertrophy (19), h...

show abstract

“…All these endogenous redox components can modify RyR function . Additionally, RyR channels are highly susceptible to modification by other endogenous redox agents, including glutathione (GSH), glutathione disulphide (GSSG), NADH, and by changes in the GSH/GSSG ratio (reviewed in Hidalgo et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Cross talk between Ca²⁺and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca²⁺release channels

Hidalgo

2005

Phil. Trans. R. Soc. B

Self Cite

View full text Add to dashboard Cite

Calcium release mediated by the ryanodine receptors (RyR) Ca 2C release channels is required for muscle contraction and contributes to neuronal plasticity. In particular, Ca 2C activation of RyRmediated Ca 2C release can amplify and propagate Ca 2C signals initially generated by Ca 2C entry into cells. Redox modulation of RyR function by a variety of non-physiological or endogenous redox molecules has been reported. The effects of RyR redox modification on Ca 2C release in skeletal muscle as well as the activation of signalling cascades and transcription factors in neurons will be reviewed here. Specifically, the different effects of S-nitrosylation or S-glutathionylation of RyR cysteines by endogenous redox-active agents on the properties of skeletal muscle RyRs will be discussed. Results will be presented indicating that these cysteine modifications change the activity of skeletal muscle RyRs, modify their behaviour towards both activators and inhibitors and affect their interactions with FKBP12 and calmodulin. In the hippocampus, sequential activation of ERK1/2 and CREB is a requisite for Ca 2C -dependent gene expression associated with long-lasting synaptic plasticity. The effects of reactive oxygen/nitrogen species on RyR channels from neurons and RyR-mediated sequential activation of neuronal ERK1/2 and CREB produced by hydrogen peroxide and other stimuli will be discussed as well.

show abstract

Redox regulation of RyR-mediated Ca2+ release in muscle and neurons

Cited by 61 publications

References 0 publications

Cross-talk between calcium and reactive oxygen species signaling

Cross-talk between calcium and reactive oxygen species signaling

Redox Sensitivity of the Ryanodine Receptor Interaction with FK506-binding Protein

Cross talk between Ca²⁺and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca²⁺release channels

Contact Info

Product

Resources

About

Redox regulation of RyR-mediated Ca2+ release in muscle and neurons

Cited by 61 publications

References 0 publications

Cross-talk between calcium and reactive oxygen species signaling

Cross-talk between calcium and reactive oxygen species signaling

Redox Sensitivity of the Ryanodine Receptor Interaction with FK506-binding Protein

Cross talk between Ca2+and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca2+release channels

Contact Info

Product

Resources

About

Cross talk between Ca²⁺and redox signalling cascades in muscle and neurons through the combined activation of ryanodine receptors/Ca²⁺release channels