A Decoy Peptide Selectively Inhibiting Dephosphorylation of Phospholamban
DC Field | Value | Language |
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dc.contributor.author | Park, Woo Jin | - |
dc.contributor.author | Oh, Jae Gyun | - |
dc.contributor.author | Jeong, Dongtak | - |
dc.contributor.author | Hajjar, Roger J. | - |
dc.date.accessioned | 2021-06-23T06:53:37Z | - |
dc.date.available | 2021-06-23T06:53:37Z | - |
dc.date.issued | 2012-08 | - |
dc.identifier.issn | 0009-7330 | - |
dc.identifier.issn | 1524-4571 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/32199 | - |
dc.description.abstract | Cardiac sarcoplasmic reticulum Ca2+ ATPase (SERCA2a) plays a crucial role in Ca2+ handling in cardiomyocytes. Phospholamban (PLB) is an endogenous inhibitor of SERCA2a and its inhibitory activity is enhanced by dephosphorylation by protein phosphatase 1 (PP1). Therefore, blocking PP1-mediated dephosphorylation of PLB would be an efficient strategy for restoration of the reduced SERCA2a activity in failing hearts. We sought to develop a decoy peptide that mimics the phosphorylated PLB and thus competitively inhibits the PP1-mediated dephosphorylation of PLB. The phosphorylation sites, Ser16 and Thr17, are located within the flexible extra-membrane loop (amino acids 14-22) of PLB. We therefore synthesized a 9-mer pseudo-phosphorylated peptide derived from this region with a replacement of Ser16 with Glu (ψ-PLB-SE). Two other 9-mer peptides with wild type PLB sequence (ψ-PLB) or with a replacement of Ser16 with Ala (ψ-PLB-SA) were also synthesized. These peptides were coupled to a cell-permeable peptide TAT to facilitate cellular uptake. Treatment of adult rat cardiomyocytes with TAT-ψ-PLB-SE, but not with TAT-ψ-PLB or TAT-ψ-PLB-SA, significantly elevated the phosphorylation level of PLB, concomitant with an increase in contractile parameters in vitro. Perfusion of isolated rat hearts with TAT-ψ-PLB-SE significantly restored the left ventricular developed pressure that was suppressed by ischemia-reperfusion (Fig. 1). These data indicate that ψ-PLB-SE prevented dephosphorylation of PLB by acting as a decoy for PP1 and it would provide effective modality to regulate SERCA2a activity in failing hearts. | - |
dc.language | 영어 | - |
dc.language.iso | ENG | - |
dc.publisher | Lippincott Williams & Wilkins Ltd. | - |
dc.title | A Decoy Peptide Selectively Inhibiting Dephosphorylation of Phospholamban | - |
dc.type | Article | - |
dc.publisher.location | 미국 | - |
dc.identifier.doi | 10.1161/res.111.suppl_1.a38 | - |
dc.identifier.wosid | 000312506400036 | - |
dc.identifier.bibliographicCitation | Circulation Research, v.111, no.4 | - |
dc.citation.title | Circulation Research | - |
dc.citation.volume | 111 | - |
dc.citation.number | 4 | - |
dc.type.docType | Meeting Abstract | - |
dc.description.isOpenAccess | N | - |
dc.description.journalRegisteredClass | sci | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Cardiovascular System & Cardiology | - |
dc.relation.journalResearchArea | Hematology | - |
dc.relation.journalWebOfScienceCategory | Cardiac & Cardiovascular Systems | - |
dc.relation.journalWebOfScienceCategory | Hematology | - |
dc.relation.journalWebOfScienceCategory | Peripheral Vascular Disease | - |
dc.subject.keywordAuthor | Heart failure | - |
dc.subject.keywordAuthor | Contractility | - |
dc.subject.keywordAuthor | Phospholamban | - |
dc.identifier.url | https://www.ahajournals.org/doi/10.1161/res.111.suppl_1.A38 | - |
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