کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8474052 | 1550418 | 2015 | 26 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
STIM1 elevation in the heart results in aberrant Ca2Â + handling and cardiomyopathy
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کلمات کلیدی
TrpSerca2L-type Ca2 + channelStore-operated Ca2 + entryBDMLTCCCMFANGIISOCESTIM1RyRCaMKIINFATCPATAC2,3-Butanedione monoxime - 2،3-Butanedione monoximeCa2 +/calmodulin-dependent protein kinase II - Ca2 + / calmodulin وابسته پروتئین کیناز IIAngiotensin II - آنژیوتانسین دوCyclopiazonic acid - اسید سیکلوپیاازونیکexcitation–contraction - تحریک-انقباضTransgenic - تراریختهTransgenesis - ترانس ژنزtransverse aortic constriction - تنگی عرضی آئورتSarcoplasmic reticulum - رتیکولوم سارکوپلاسمیکendoplasmic reticulum - شبکه آندوپلاسمی nuclear factor of activated T-cells - عامل هسته سلول های فعال شده فعال استphenylephrine - فنیل آفرینStromal interaction molecule 1 - مولکول تعامل استروما 1Cardiac myocytes - میوکسی های قلبیheart failure - نارسایی قلبیwild-type - نوع وحشیHypertrophy - هیپرتروفی یا پُرسازیtransient receptor potential - پتانسیل گیرنده گذراCalcium - کلسیمRyanodine receptor - گیرنده رایانودین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Stromal interaction molecule 1 (STIM1) is a Ca2Â + sensor that partners with Orai1 to elicit Ca2Â + entry in response to endoplasmic reticulum (ER) Ca2Â + store depletion. While store-operated Ca2Â + entry (SOCE) is important for maintaining ER Ca2Â + homeostasis in non-excitable cells, it is unclear what role it plays in the heart, although STIM1 is expressed in the heart and upregulated during disease. Here we analyzed transgenic mice with STIM1 overexpression in the heart to model the known increase of this protein in response to disease. As expected, STIM1 transgenic myocytes showed enhanced Ca2Â + entry following store depletion and partial co-localization with the type 2 ryanodine receptor (RyR2) within the sarcoplasmic reticulum (SR), as well as enrichment around the sarcolemma. STIM1 transgenic mice exhibited sudden cardiac death as early as 6Â weeks of age, while mice surviving past 12Â weeks of age developed heart failure with hypertrophy, induction of the fetal gene program, histopathology and mitochondrial structural alterations, loss of ventricular functional performance and pulmonary edema. Younger, pre-symptomatic STIM1 transgenic mice exhibited enhanced pathology following pressure overload stimulation or neurohumoral agonist infusion, compared to controls. Mechanistically, cardiac myocytes isolated from STIM1 transgenic mice displayed spontaneous Ca2Â + transients that were prevented by the SOCE blocker SKF-96365, increased L-type Ca2Â + channel (LTCC) current, and enhanced Ca2Â + spark frequency. Moreover, adult cardiac myocytes from STIM1 transgenic mice showed both increased diastolic Ca2Â + and maximal transient amplitude but no increase in total SR Ca2Â + load. Associated with this enhanced Ca2Â + profile was an increase in cardiac nuclear factor of activated T-cells (NFAT) and Ca2Â +/calmodulin-dependent kinase II (CaMKII) activity. We conclude that STIM1 has an unexpected function in the heart where it alters communication between the sarcolemma and SR resulting in greater Ca2Â + flux and a leaky SR compartment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Molecular and Cellular Cardiology - Volume 87, October 2015, Pages 38-47
Journal: Journal of Molecular and Cellular Cardiology - Volume 87, October 2015, Pages 38-47
نویسندگان
Robert N. Correll, Sanjeewa A. Goonasekera, Jop H. van Berlo, Adam R. Burr, Federica Accornero, Hongyu Zhang, Catherine A. Makarewich, Allen J. York, Michelle A. Sargent, Xiongwen Chen, Steven R. Houser, Jeffery D. Molkentin,