کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8772574 | 1599137 | 2018 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Protein carbamylation exacerbates vascular calcification
ترجمه فارسی عنوان
کربامیلاسیون پروتئین، کلسیفیکاسیون عروقی را تشدید می کند
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کلمات کلیدی
استرس اکسیداتیو، اوره، کلسیفیکاسیون عروقی،
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
چکیده انگلیسی
Protein carbamylation is a posttranslational modification that can occur non-enzymatically in the presence of high concentrations of urea. Although carbamylation is recognized as a prognostic biomarker, the contribution of protein carbamylation to organ dysfunction remains uncertain. Because vascular calcification is common under carbamylation-prone situations, we investigated the effects of carbamylation on this pathologic condition. Protein carbamylation exacerbated the calcification of human vascular smooth muscle cells (hVSMCs) by suppressing the expression of ectonucleotide pyrophosphate/phosphodiesterase 1 (ENPP1), a key enzyme in the generation of pyrophosphate, which is a potent inhibitor of ectopic calcification. Several mitochondrial proteins were carbamylated, although ENPP1 itself was not identified as a carbamylated protein. Rather, protein carbamylation reduced mitochondrial membrane potential and exaggerated mitochondria-derived oxidative stress, which down-regulated ENPP1. The effects of carbamylation on ectopic calcification were abolished in hVSMCs by ENPP1 knockdown, in mitochondrial-DNA-depleted hVSMCs, and in hVSMCs treated with a mitochondria-targeted superoxide scavenger. We also evaluated the carbamylation effects using ex vivo and in vivo models. The tunica media of a patient with end-stage renal disease was carbamylated. Thus, our findings have uncovered a previously unrecognized aspect of uremia-related vascular pathology.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 94, Issue 1, July 2018, Pages 72-90
Journal: Kidney International - Volume 94, Issue 1, July 2018, Pages 72-90
نویسندگان
Daisuke Mori, Isao Matsui, Akihiro Shimomura, Nobuhiro Hashimoto, Ayumi Matsumoto, Karin Shimada, Satoshi Yamaguchi, Tatsufumi Oka, Keiichi Kubota, Sayoko Yonemoto, Yusuke Sakaguchi, Atsushi Takahashi, Yasunori Shintani, Seiji Takashima,