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Endoplasmic reticulum resident protein 44 (ERp44) deficiency in mice and zebrafish leads to cardiac developmental and functional defects.
Wang, Ding-Yan; Abbasi, Cynthia; El-Rass, Suzan; Li, Jamie Yuanjun; Dawood, Fayez; Naito, Kotaro; Sharma, Parveen; Bousette, Nicolas; Singh, Shalini; Backx, Peter H; Cox, Brian; Wen, Xiao-Yan; Liu, Peter P; Gramolini, Anthony O.
Afiliação
  • Wang DY; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Abbasi C; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • El-Rass S; Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.) Keenan Research Center for Biomedical Science and Zebrafish Center for Advanced Drug Discovery, Li Ka Shing Knowledge Institute, St. Michael's Hospital, T
  • Li JY; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Dawood F; Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.).
  • Naito K; Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.).
  • Sharma P; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Bousette N; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Singh S; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Backx PH; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.) Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.).
  • Cox B; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.).
  • Wen XY; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.) Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.) Keenan Res
  • Liu PP; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.) Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.).
  • Gramolini AO; Department of Physiology, University of Toronto, Ontario, Canada (D.Y.W., C.A., J.Y.L., P.S., N.B., S.S., P.H.B., B.C., X.Y.W., P.P.L., A.O.G.) Faculty of Medicine and Institute of Medical Science, University of Toronto, Ontario, Canada (S.E.R., F.D., K.N., P.H.B., X.Y.W., P.P.L., A.O.G.).
J Am Heart Assoc ; 3(5): e001018, 2014 Oct 20.
Article em En | MEDLINE | ID: mdl-25332179
ABSTRACT

BACKGROUND:

Endoplasmic reticulum (ER) resident protein 44 (ERp44) is a member of the protein disulfide isomerase family, is induced during ER stress, and may be involved in regulating Ca(2+) homeostasis. However, the role of ERp44 in cardiac development and function is unknown. The aim of this study was to investigate the role of ERp44 in cardiac development and function in mice, zebrafish, and embryonic stem cell (ESC)-derived cardiomyocytes to determine the underlying role of ERp44. METHODS AND

RESULTS:

We generated and characterized ERp44(-/-) mice, ERp44 morphant zebrafish embryos, and ERp44(-/-) ESC-derived cardiomyocytes. Deletion of ERp44 in mouse and zebrafish caused significant embryonic lethality, abnormal heart development, altered Ca(2+) dynamics, reactive oxygen species generation, activated ER stress gene profiles, and apoptotic cell death. We also determined the cardiac phenotype in pressure overloaded, aortic-banded ERp44(+/-) mice enhanced ER stress activation and increased mortality, as well as diastolic cardiac dysfunction with a significantly lower fractional shortening. Confocal and LacZ histochemical staining showed a significant transmural gradient for ERp44 in the adult heart, in which high expression of ERp44 was observed in the outer subepicardial region of the myocardium.

CONCLUSIONS:

ERp44 plays a critical role in embryonic heart development and is crucial in regulating cardiac cell Ca(2+) signaling, ER stress, ROS-induced oxidative stress, and activation of the intrinsic mitochondrial apoptosis pathway.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Chaperonas Moleculares / Proteínas de Peixe-Zebra / Miócitos Cardíacos / Retículo Endoplasmático / Células-Tronco Embrionárias / Cardiopatias Congênitas / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Chaperonas Moleculares / Proteínas de Peixe-Zebra / Miócitos Cardíacos / Retículo Endoplasmático / Células-Tronco Embrionárias / Cardiopatias Congênitas / Proteínas de Membrana Limite: Animals Idioma: En Ano de publicação: 2014 Tipo de documento: Article