کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6161977 | 1249381 | 2015 | 14 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
High-mobility group box 1 is a novel deacetylation target of Sirtuin1
ترجمه فارسی عنوان
گروه جعبه 1 گروه تحریر: یک هدف جدید برای حذف سیتیلین است
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کلمات کلیدی
نارسایی حاد کلیه، سلول های اندوتلیال، ایسکمی-رپرفیوژن، فیزیولوژی کلیوی،
موضوعات مرتبط
علوم پزشکی و سلامت
پزشکی و دندانپزشکی
بیماریهای کلیوی
چکیده انگلیسی
High-mobility group box 1 (HMGB1) undergoes acetylation, nuclear-to-cytoplasmic translocation, and release from stressed kidneys, unleashing a signaling cascade of events leading to systemic inflammation. Here, we tested whether the deacetylase activity of Sirtuin1 (SIRT1) participates in regulating nuclear retention of HMGB1 to ultimately modulate damage signaling initiated by HMGB1 secretion during stress. When immunoprecipitated acetylated HMGB1 was incubated with SIRT1, HMGB1 acetylation decreased by 57%. Proteomic analysis showed that SIRT1 deacetylates HMGB1 at four lysine residues (55, 88, 90, and 177) within the proinflammatory and nuclear localization signal domains of HMGB1. Genetic ablation or pharmacological inhibition of SIRT1 in endothelial cells increased HMGB1 acetylation and translocation. In vivo, deletion of SIRT1 reduced nuclear HMGB1 while increasing its acetylation and release into circulation during basal and ischemic conditions, causing increased renal damage. Conversely, resveratrol pretreatment led to decreased HMGB1 acetylation, its nuclear retention, decreased systemic release, and reduced tubular damage. Thus, a vicious cycle is set into motion in which the inflammation-induced repression of SIRT1 disables deacetylation of HMGB1, facilitates its nuclear-to-cytoplasmic translocation, and systemic release, thereby maintaining inflammation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Kidney International - Volume 87, Issue 1, January 2015, Pages 95-108
Journal: Kidney International - Volume 87, Issue 1, January 2015, Pages 95-108
نویسندگان
May M. Rabadi, Sandhya Xavier, Radovan Vasko, Kavneet Kaur, Michael S. Goligorksy, Brian B. Ratliff,