کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5859030 | 1562323 | 2015 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Gene expression profiling identifies the novel role of immunoproteasome in doxorubicin-induced cardiotoxicity
ترجمه فارسی عنوان
پروفیل بیان ژن، نقش جدید ایمونو پروتئازوم را در سمیت قلبی ناشی از دوکسوروبیسین مشخص می کند
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کلمات کلیدی
ubiquitin conjugating enzymesE3SDOXE1SE2SDeubiquitinasesDUBs - DUB هاROS - ROSImmunoproteasome - ایمونو پروتئازومApoptosis - خزان یاختهایDoxorubicin - دوکسوروبیسینMicroarray - ریزآرایهCardiotoxicity - سمیت قلبیUbiquitin-proteasome system - سیستم Ubiquitin-proteasomeubiquitin ligases - لیگاز ubiquitinReactive oxygen species - گونههای فعال اکسیژنUPS - یو پی اس
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
چکیده انگلیسی
The most well-known cause of chemotherapy-induced cardiotoxicity is doxorubicin (DOX). The ubiquitin-proteasome system (UPS) is the main cellular machinery for protein degradation in eukaryotic cells. However, the expression pattern of the UPS in DOX-induced cardiotoxicity remains unclear. C57BL/6 mice were intraperitoneally injected with a single dose of DOX (15 mg/kg). After 1, 3 and 5 days, cardiac function and apoptosis were detected with echocardiography and TUNEL assay. Microarray assay and qPCR analysis were also performed at day 5. We found that DOX caused a significant decrease in cardiac function at day 5 and increase in cardiomyocyte apoptosis at days 3 and 5. Microarray data revealed that totally 1185 genes were significantly regulated in DOX-treated heart, and genes involved in apoptosis and the UPS were mostly altered. Among them, the expression of 3 immunoproteasome catalytic subunits (β1i, β2i and β5i) was markedly down-regulated. Moreover, DOX significantly decreased proteasome activities and enhanced polyubiquitinated proteins in the heart. Importantly, overexpression of immunoproteasome catalytic subunits (β1i, β2i or β5i) significantly attenuated DOX-induced cardiomyocyte apoptosis and other UPS gene expression while knockdown of them significantly increased DOX-induced cardiomyocyte apoptosis. These effects were partially associated with increased degradation of multiple pro-apoptotic proteins. In conclusion, our studies suggest that immunoproteasome plays an important role in DOX-induced cardiomyocyte apoptosis, and may be a novel therapeutic target for prevention of DOX-induced cardiotoxicity.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 333, 3 July 2015, Pages 76-88
Journal: Toxicology - Volume 333, 3 July 2015, Pages 76-88
نویسندگان
Wen-Jie Zhao, Sheng-Nan Wei, Xiang-Jun Zeng, Yun-Long Xia, Jie Du, Hui-Hua Li,