کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8294394 | 1536751 | 2018 | 23 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Selective degradation of BET proteins with dBET1, a proteolysis-targeting chimera, potently reduces pro-inflammatory responses in lipopolysaccharide-activated microglia
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
TBSNuclear Factor- κBBET proteinsTBSTTLRIL-1βBRDiNOSCOX-2NF-κBshRNAMMPTNFαLPSCCL2RNA polymerase II - آرانای پلیمراز II DMSO - DMSOshort hairpin RNA - RNA موی سر کوتاهinflammation - التهاب( توروم) interleukin-1 β - اینترلوکین-1βTris-buffered saline - تریس بافر شورtumor necrosis factor alpha - تومور نکروز عامل آلفاToll-like receptor - تیالآرDimethyl sulfoxide - دیمتیل سولفواکسیدinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییCyclooxygenase-2 - سیکلوکوکسیژناز2BET - شرطlipopolysaccharide - لیپوپلی ساکاریدmatrix metalloproteinase - ماتریکس متالوپروتئینازMicroglia - میکروگلیاهاPol II - پل دومchemokine (C-C motif) ligand 2 - کیموکین (C-C motif) لیگاند 2
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Bromodomain and extraterminal (BET) proteins are essential to pro-inflammatory gene transcription. The BET family proteins, BRD2, BRD3, BRD4, and testis-specific BRDT, couple chromatin remodeling to gene transcription, acting as histone acetyltransferases, scaffolds for transcription complexes, and markers of histone acetylation. To initiate an inflammatory response, cells undergo de novo gene transcription requiring histone-modifying proteins to make DNA wrapped around histones more or less readily available to transcription complexes. Because BET proteins are the gatekeepers of nuclear factor-κB (NF-κB)-dependent gene transcription, we hypothesized that degradation of BET proteins, particularly BRD2 and BRD4, with the proteolysis-targeting chimera (PROTAC) dBET1 would dampen the pro-inflammatory response in microglia subjected to lipopolysaccharide (LPS) challenge. Degradation of BRD2 and BRD4 was associated with significantly reduced expression of several pro-inflammatory genes: inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin (IL)-1β, tumor necrosis factor-a (TNF-α), IL-6, chemokine (C-C motif) ligand 2 (CCL2), and matrix metalloproteinase-9 (MMP-9). This is the first study showing that dBET1-mediated targeted degradation of BET proteins robustly dampens pro-inflammatory responses in LPS-stimulated microglia. These data suggest that BET degradation with dBET1 will likely reduce expression of pro-inflammatory genes in in vivo neuroinflammatory models associated with microglial/immune cell activation.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 1, 26 February 2018, Pages 410-415
Journal: Biochemical and Biophysical Research Communications - Volume 497, Issue 1, 26 February 2018, Pages 410-415
نویسندگان
Kelly M. DeMars, Changjun Yang, Carolina I. Castro-Rivera, Eduardo Candelario-Jalil,