کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2079159 1545072 2015 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوتکنولوژی یا زیست‌فناوری
پیش نمایش صفحه اول مقاله
P2X4 receptor–eNOS signaling pathway in cardiac myocytes as a novel protective mechanism in heart failure
چکیده انگلیسی

We have demonstrated using immunoprecipitation and immunostaining a novel physical association of the P2X4 receptor (P2X4R), a ligand-gated ion channel, with the cardioprotective, calcium-dependent enzyme endothelial nitric oxide synthase (eNOS). Treatment of murine ventricular myocytes with the P2XR agonist 2-methylthioATP (2-meSATP) to induce a current (mainly Na+) increased the formation of nitric oxide (NO), as measured using a fluorescent probe. Possible candidates for downstream effectors mediating eNOS activity include cyclic GMP and PKG or cellular protein nitrosylation. A cardiac-specific P2X4R overexpressing mouse line was protected from heart failure (HF) with improved cardiac function and survival in post-infarct, pressure overload, and calsequestrin (CSQ) overexpression models of HF. Although the role of the P2X4R in other tissues such as the endothelium and monocytes awaits characterization in tissue-specific KO, cardiac-specific activation of eNOS may be more cardioprotective than an increased activity of global systemic eNOS. The intra-myocyte formation of NO may be more advantageous over NO derived externally from a donor. A small molecule drug stimulating this sarcolemmal pathway or gene therapy-mediated overexpression of the P2X4R in cardiac myocytes may represent a new therapy for both ischemic and pressure overloaded HF.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Computational and Structural Biotechnology Journal - Volume 13, 2015, Pages 1–7
نویسندگان
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