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Article: The sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load

TitleThe sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load
Authors
KeywordsDisulfide bonds
Heart failure
Endoplasmic reticulum
Issue Date2011
Citation
FASEB Journal, 2011, v. 25, n. 8, p. 2583-2591 How to Cite?
AbstractTwo related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in the mammalian endoplasmic reticulum (ER). Redox changes in cysteine residues on intralumenal loops of calcium release and reuptake channels have been implicated in altered calcium release and reuptake. These findings led us to hypothesize that altered ERO1 activity may affect cardiac functions that are dependent on intracellular calcium flux. We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β. The peak amplitude of calcium transients in homozygous Ero1α mutant adult cardiomyocytes was reduced to 42.0 ± 2.2% (n=10, P≤0.01) of values recorded in wild-type cardiomyocytes. Decreased ERO1 activity blunted cardiomyocyte inotropic response to adrenergic stimulation and sensitized mice to adrenergic blockade. Whereas all 12 wild-type mice survived challenge with 4 mg/kg esmolol, 6 of 8 compound Ero1l and Ero1lb mutant mice succumbed to this level of β adrenergic blockade (P≤0.01). In addition, mice lacking ERO1α were partially protected against progressive heart failure in a transaortic constriction model [at 10 wk postprocedure, fractional shortening was 0.31±0.02 in the mutant (n=20) vs. 0.23±0.03 in the wild type (n=18); P≤0.01]. These findings establish a role for ERO1 in calcium homeostasis and suggest that modifying the lumenal redox environment may affect the progression of heart failure.
Persistent Identifierhttp://hdl.handle.net/10722/205747
ISSN
2015 Impact Factor: 5.299
2015 SCImago Journal Rankings: 2.775
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChin, Kingtung-
dc.contributor.authorKang, Guoxin-
dc.contributor.authorQu, Jiaxiang-
dc.contributor.authorGardner, Lawrence B.-
dc.contributor.authorCoetzee, William A.-
dc.contributor.authorZito, Ester-
dc.contributor.authorFishman, Glenn I.-
dc.contributor.authorRon, David-
dc.date.accessioned2014-10-06T08:02:18Z-
dc.date.available2014-10-06T08:02:18Z-
dc.date.issued2011-
dc.identifier.citationFASEB Journal, 2011, v. 25, n. 8, p. 2583-2591-
dc.identifier.issn0892-6638-
dc.identifier.urihttp://hdl.handle.net/10722/205747-
dc.description.abstractTwo related ER oxidation 1 (ERO1) proteins, ERO1α and ERO1β, dynamically regulate the redox environment in the mammalian endoplasmic reticulum (ER). Redox changes in cysteine residues on intralumenal loops of calcium release and reuptake channels have been implicated in altered calcium release and reuptake. These findings led us to hypothesize that altered ERO1 activity may affect cardiac functions that are dependent on intracellular calcium flux. We established mouse lines with loss of function insertion mutations in Ero1l and Ero1lb encoding ERO1α and ERO1β. The peak amplitude of calcium transients in homozygous Ero1α mutant adult cardiomyocytes was reduced to 42.0 ± 2.2% (n=10, P≤0.01) of values recorded in wild-type cardiomyocytes. Decreased ERO1 activity blunted cardiomyocyte inotropic response to adrenergic stimulation and sensitized mice to adrenergic blockade. Whereas all 12 wild-type mice survived challenge with 4 mg/kg esmolol, 6 of 8 compound Ero1l and Ero1lb mutant mice succumbed to this level of β adrenergic blockade (P≤0.01). In addition, mice lacking ERO1α were partially protected against progressive heart failure in a transaortic constriction model [at 10 wk postprocedure, fractional shortening was 0.31±0.02 in the mutant (n=20) vs. 0.23±0.03 in the wild type (n=18); P≤0.01]. These findings establish a role for ERO1 in calcium homeostasis and suggest that modifying the lumenal redox environment may affect the progression of heart failure.-
dc.languageeng-
dc.relation.ispartofFASEB Journal-
dc.subjectDisulfide bonds-
dc.subjectHeart failure-
dc.subjectEndoplasmic reticulum-
dc.titleThe sarcoplasmic reticulum luminal thiol oxidase ERO1 regulates cardiomyocyte excitation-coupled calcium release and response to hemodynamic load-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1096/fj.11-184622-
dc.identifier.pmid21507899-
dc.identifier.scopuseid_2-s2.0-80051704067-
dc.identifier.volume25-
dc.identifier.issue8-
dc.identifier.spage2583-
dc.identifier.epage2591-
dc.identifier.eissn1530-6860-
dc.identifier.isiWOS:000293337800009-

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