کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8289325 | 1536302 | 2016 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca2+-sensitivity and suppress the modulation of Ca2+-sensitivity by troponin I phosphorylation
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کلمات کلیدی
DCMIn vitro motility assayHCMEpigallocatechin-3-gallateEGCGTNCTnI - TNITroponin C - تروپونین CTroponin I - تروپونین ITroponin T - تروپونین TTnT - تی ان تیHill coefficient - ضریب هیلRate of force development - نرخ نیروی توسعهwild-type - نوع وحشیDilated cardiomyopathy - کاردیومیوپاتی دیلاته، کاردیومیوپاتی کاملHypertrophic cardiomyopathy - کاردیومیوپاتی هایپرتروفیک kact - ککت
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca2+-sensitivity and suppress the modulation of Ca2+-sensitivity by troponin I phosphorylation Mutations in troponin T associated with Hypertrophic Cardiomyopathy increase Ca2+-sensitivity and suppress the modulation of Ca2+-sensitivity by troponin I phosphorylation](/preview/png/8289325.png)
چکیده انگلیسی
We investigated the effect of 7 Hypertrophic Cardiomyopathy (HCM)-causing mutations in troponin T (TnT) on troponin function in thin filaments reconstituted with actin and human cardiac tropomyosin. We used the quantitative in vitro motility assay to study Ca2+-regulation of unloaded movement and its modulation by troponin I phosphorylation. Troponin from a patient with the K280N TnT mutation showed no difference in Ca2+-sensitivity when compared with donor heart troponin and the Ca2+-sensitivity was also independent of the troponin I phosphorylation level (uncoupled). The recombinant K280N TnT mutation increased Ca2+-sensitivity 1.7-fold and was also uncoupled. The R92Q TnT mutation in troponin from transgenic mouse increased Ca2+-sensitivity and was also completely uncoupled. Five TnT mutations (Î14, Î28 + 7, ÎE160, S179F and K273E) studied in recombinant troponin increased Ca2+-sensitivity and were all fully uncoupled. Thus, for HCM-causing mutations in TnT, Ca2+-sensitisation together with uncoupling in vitro is the usual response and both factors may contribute to the HCM phenotype. We also found that Epigallocatechin-3-gallate (EGCG) can restore coupling to all uncoupled HCM-causing TnT mutations. In fact the combination of Ca2+-desensitisation and re-coupling due to EGCG completely reverses both the abnormalities found in troponin with a TnT HCM mutation suggesting it may have therapeutic potential.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Archives of Biochemistry and Biophysics - Volume 601, 1 July 2016, Pages 113-120
Journal: Archives of Biochemistry and Biophysics - Volume 601, 1 July 2016, Pages 113-120
نویسندگان
Andrew E. Messer, Christopher R. Bayliss, Mohammed El-Mezgueldi, Charles S. Redwood, Douglas G. Ward, Man-Ching Leung, Maria Papadaki, Cristobal dos Remedios, Steven B. Marston,