کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2165930 1091791 2013 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calcium dysregulation in ventricular myocytes from mice expressing constitutively active Rac1
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Calcium dysregulation in ventricular myocytes from mice expressing constitutively active Rac1
چکیده انگلیسی

Increased Rac1 activity and its concomitant elevation of reactive oxygen species (ROS) levels is believed to be involved in the development of cardiac diseases such as hypertrophy and arrhythmia. To study the effects of activated Rac1 on the properties of isolated ventricular myocytes we used a transgenic mouse model (RacET) expressing constitutively active Rac1. Concurrent with dilated cardiomyopathy global Ca2+ handling as well as single cell contractility was substantially decreased. Cellular ROS levels were assessed with two independent assays and unexpectedly depicted decreased ROS production in RacET that was uncoupled from hormonal stimulation. Western blot analysis illustrated a massive increase in cellular Rac1 activity concomitant with a reduction in NADPH-oxidase activity. Analysis of the Ca2+ current, the ryanodine receptor and fractional Ca2+ release uncovered defective excitation–contraction (ec) coupling and a substantial increase in sarcoplasmic reticulum Ca2+ leak together with a larger Ca2+ spark amplitude and frequency. We conclude that Rac1 activity plays an important role for cardiac diseases but can be uncoupled from NADPH-oxidase activity. Rac1-mediated partial uncoupling of the ec-coupling machinery results in a ROS-independent disarrayed cellular Ca2+ handling, contractility and impaired cardiac function.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cell Calcium - Volume 54, Issue 1, July 2013, Pages 26–36
نویسندگان
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