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Endoplasmic reticulum resident protein 44 (ERp44) deficiency in mice and zebrafish leads to cardiac developmental and functional defects
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نویسنده
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wang d.-y. ,abbasi c. ,el-rass s. ,li j.y. ,dawood f. ,naito k. ,sharma p. ,bousette n. ,singh s. ,backx p.h. ,cox b. ,wen x.-y. ,liu p.p. ,gramolini a.o.
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منبع
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journal of the american heart association - 2014 - دوره : 3 - شماره : 5
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چکیده
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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 ca2+ 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 ca2+ 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 ca2+ signaling,er stress,ros-induced oxidative stress,and activation of the intrinsic mitochondrial apoptosis pathway. © 2014 the authors. published on behalf of the american heart association,inc.,by wiley blackwell.
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کلیدواژه
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apoptosis; Ca2+; ERp44-/-; ESC-derived cardiomyocytes; Heart development and cardiomyopathy
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آدرس
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department of physiology,university of torontoon, Canada, department of physiology,university of torontoon, Canada, faculty of medicine and institute of medical science,university of torontoon,canada,keenan research center for biomedical science and zebrafish center for advanced drug discovery,li ka shing knowledge institute,st. michael's hospital,toronto,on, Canada, department of physiology,university of torontoon, Canada, faculty of medicine and institute of medical science,university of torontoon, Canada, faculty of medicine and institute of medical science,university of torontoon, Canada, department of physiology,university of torontoon, Canada, department of physiology,university of torontoon,canada,montreal heart institute,montrealqc, Canada, department of physiology,university of torontoon, Canada, department of physiology,university of torontoon,canada,faculty of medicine and institute of medical science,university of torontoon, Canada, department of physiology,university of torontoon, Canada, department of physiology,university of torontoon,canada,faculty of medicine and institute of medical science,university of torontoon,canada,keenan research center for biomedical science and zebrafish center for advanced drug discovery,li ka shing knowledge institute,st. michael's hospital,toronto,on, Canada, department of physiology,university of torontoon,canada,faculty of medicine and institute of medical science,university of torontoon,canada,university of ottawa heart institute,ottawa,on, Canada, department of physiology,university of torontoon,canada,faculty of medicine and institute of medical science,university of torontoon, Canada
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Authors
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