کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8344735 | 1541588 | 2018 | 45 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A sense oligonucleotide to inducible nitric oxide synthase mRNA increases the survival rate of rats in septic shock
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کلمات کلیدی
asRNAquantitative reverse transcription–polymerase chain reactionAntisense transcriptsGalNLNAiNOSqRT-PCRLPS3′ untranslated region - 3 منطقه غیر ترجمه3′UTR - 3'UTRd-Galactosamine - d-گالاکتوزامینNon-coding RNA - RNA غیرکد کننده، RNA غیرترجمه شوندهLocked Nucleic Acid - اسید نوکلئیک قفل شدهEndotoxemia - اندوتوکسمیinterleukin - اینترلوکینtumor necrosis factor α - تومور نکروز عامل αTUNEL - تونلinducible nitric oxide synthase - سنتاز اکسید نیتریک القاییSepsis - سپتیسمی یا مسمومیت خونelongation factor 1α - ضریب انحنای 1αTNF-α - فاکتور نکروز توموری آلفاlipopolysaccharide - لیپوپلی ساکاریدLiver failure - نارسایی کبدNitric oxide - نیتریک اکسید
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Natural antisense transcripts (asRNAs) that do not encode proteins are transcribed from rat, mouse, and human genes, encoding inducible nitric oxide synthase (iNOS), which catalyzes the production of the inflammatory mediator nitric oxide (NO). In septic shock, NO is excessively produced in hepatocytes and macrophages. The iNOS asRNA interacts with and stabilizes iNOS mRNA. We found that single-stranded 'sense' oligonucleotides corresponding to the iNOS mRNA sequence reduced iNOS mRNA levels by interfering with the mRNA-asRNA interactions in rat hepatocytes. The iNOS sense oligonucleotides that were substituted with phosphorothioate bonds and locked nucleic acids efficiently decreased the levels of iNOS mRNA and iNOS protein. In this study, the gene expression patterns in the livers of two endotoxemia model rats with acute liver failure were compared. Next, we optimized the sequence and modification of the iNOS sense oligonucleotides in interleukin 1β-treated rat hepatocytes. When a sense oligonucleotide was simultaneously administered with d-galactosamine and bacterial lipopolysaccharide (LPS) to rats, their survival rate significantly increased compared to the rats administered d-galactosamine and LPS alone. In the livers of the sense oligonucleotide-administered rats, apoptosis in the hepatocytes markedly decreased. These results suggest that natural antisense transcript-targeted regulation technology using iNOS sense oligonucleotides may be used to treat human inflammatory diseases, such as sepsis and septic shock.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Nitric Oxide - Volume 72, 30 January 2018, Pages 32-40
Journal: Nitric Oxide - Volume 72, 30 January 2018, Pages 32-40
نویسندگان
Tetsuya Okuyama, Richi Nakatake, Masaki Kaibori, Tadayoshi Okumura, Masanori Kon, Mikio Nishizawa,