AAV-Mediated Knock-Down of HRC Exacerbates Transverse Aorta Constriction-Induced Heart Failure
DC Field | Value | Language |
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dc.contributor.author | Park, Chang Sik | - |
dc.contributor.author | Cha, Hyeseon | - |
dc.contributor.author | Kwon, Eun Jeong | - |
dc.contributor.author | Jeong, Dongtak | - |
dc.contributor.author | Hajjar, Roger J. | - |
dc.contributor.author | Kranias, Evangelia G. | - |
dc.contributor.author | Cho, Chunghee | - |
dc.contributor.author | Park, Woo Jin | - |
dc.contributor.author | Kim, Do Han | - |
dc.date.accessioned | 2021-06-23T06:53:12Z | - |
dc.date.available | 2021-06-23T06:53:12Z | - |
dc.date.created | 2021-01-21 | - |
dc.date.issued | 2012-08 | - |
dc.identifier.issn | 1932-6203 | - |
dc.identifier.uri | https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/32186 | - |
dc.description.abstract | Background: Histidine-rich calcium binding protein (HRC) is located in the lumen of sarcoplasmic reticulum (SR) that binds to both triadin (TRN) and SERCA affecting Ca2+ cycling in the SR. Chronic overexpression of HRC that may disrupt intracellular Ca2+ homeostasis is implicated in pathogenesis of cardiac hypertrophy. Ablation of HRC showed relatively normal phenotypes under basal condition, but exhibited a significantly increased susceptibility to isoproterenol-induced cardiac hypertrophy. In the present study, we characterized the functions of HRC related to Ca2+ cycling and pathogenesis of cardiac hypertrophy using the in vitro siRNA-and the in vivo adeno-associated virus (AAV)-mediated HRC knock-down (KD) systems, respectively. Methodology/Principal Findings: AAV-mediated HRC-KD system was used with or without C57BL/6 mouse model of transverse aortic constriction-induced failing heart (TAC-FH) to examine whether HRC-KD could enhance cardiac function in failing heart (FH). Initially we expected that HRC-KD could elicit cardiac functional recovery in failing heart (FH), since predesigned siRNA-mediated HRC-KD enhanced Ca2+ cycling and increased activities of RyR2 and SERCA2 without change in SR Ca2+ load in neonatal rat ventricular cells (NRVCs) and HL-1 cells. However, AAV9-mediated HRC-KD in TAC-FH was associated with decreased fractional shortening and increased cardiac fibrosis compared with control. We found that phospho-RyR2, phospho-CaMKII, phospho-p38 MAPK, and phospho-PLB were significantly upregulated by HRC-KD in TAC-FH. A significantly increased level of cleaved caspase-3, a cardiac cell death marker was also found, consistent with the result of TUNEL assay. Conclusions/Significance: Increased Ca2+ leak and cytosolic Ca2+ concentration due to a partial KD of HRC could enhance activity of CaMKII and phosphorylation of p38 MAPK, causing the mitochondrial death pathway observed in TAC-FH. Our results present evidence that down-regulation of HRC could deteriorate cardiac function in TAC-FH through perturbed SR-mediated Ca2+ cycling. | - |
dc.language | 영어 | - |
dc.language.iso | en | - |
dc.publisher | PUBLIC LIBRARY SCIENCE | - |
dc.title | AAV-Mediated Knock-Down of HRC Exacerbates Transverse Aorta Constriction-Induced Heart Failure | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Jeong, Dongtak | - |
dc.identifier.doi | 10.1371/journal.pone.0043282 | - |
dc.identifier.scopusid | 2-s2.0-84865472735 | - |
dc.identifier.wosid | 000308213600019 | - |
dc.identifier.bibliographicCitation | PLOS ONE, v.7, no.8, pp.1 - 17 | - |
dc.relation.isPartOf | PLOS ONE | - |
dc.citation.title | PLOS ONE | - |
dc.citation.volume | 7 | - |
dc.citation.number | 8 | - |
dc.citation.startPage | 1 | - |
dc.citation.endPage | 17 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.isOpenAccess | Y | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Science & Technology - Other Topics | - |
dc.relation.journalWebOfScienceCategory | Multidisciplinary Sciences | - |
dc.subject.keywordPlus | CA2+/CALMODULIN-DEPENDENT PROTEIN-KINASE | - |
dc.subject.keywordPlus | INDUCED CARDIAC-HYPERTROPHY | - |
dc.subject.keywordPlus | CHANNEL RYANODINE RECEPTOR | - |
dc.subject.keywordPlus | CA-BINDING-PROTEIN | - |
dc.subject.keywordPlus | RICH CA2+-BINDING PROTEIN | - |
dc.subject.keywordPlus | HISTIDINE-RICH | - |
dc.subject.keywordPlus | SARCOPLASMIC-RETICULUM | - |
dc.subject.keywordPlus | SKELETAL-MUSCLE | - |
dc.subject.keywordPlus | DILATED CARDIOMYOPATHY | - |
dc.subject.keywordPlus | II PHOSPHORYLATION | - |
dc.identifier.url | https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043282 | - |
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