کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1995497 | 1064977 | 2007 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Hypoxia inducible factor-1 modulates hemin-induced IL-8 secretion in microvascular endothelium
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کلمات کلیدی
FACDMOGdimethyloxalylglycinePDTCHMEC-1Iron - آهنInterleukin-8 - اینترلوکین -8pyrrolidine dithiocarbamate - دی اتیل کربامات پیرولیدینhypoxia inducible factor-1 - عامل القایی هیپوکسی 1Erythrocyte lysis - لیزیزرژیتهHeme - هم Hemin - همینTin protoporphyrin - پروتپورپیرین قلعZinc protoporphyrin - پروپوپورفیرین رویReactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Ischemia/Reperfusion injury and hemolysis are characterized by erythrocyte lysis and release of free heme into the microcirculation. Following substantial erythrocyte lysis, heme overwhelms circulatory heme-binding protein networks rapidly forming hemin, the oxidized form of iron protoporphyrin IX. Hemin's role in modulating inflammatory responses in microvascular endothelium (MVEC) remains ill-defined. We studied the impact of hemin exposure on human MVEC interleukin-8 (IL-8) expression. Hemin significantly up-regulated MVEC IL-8 secretion and was associated with cellular iron loading. Hemin-induced IL-8 up-regulation was significantly attenuated by increasing environmental serum concentrations. As well, hemin-induced IL-8 secretion was significantly reduced in a concentration-dependent fashion following pyrrolidine dithiocarbamate exposure, suggesting that induction occurred via an oxidant-sensitive mechanism. Interestingly, transfection studies revealed that oxidant-driven transcription factors NF-κB and AP-1 played no role in hemin-induced IL-8 transcription. In studies employing actinomycin D, hemin was found to dramatically lengthen IL-8 mRNA half-life. Of major importance in the current report was the finding that hypoxia inducible factor-1 (HIF-1), a powerful transcription factor mediating tissue responses to hypoxia, potently regulated hemin-induced IL-8 secretion in human MVEC. Activation of HIF-1 via the prolyl hydroxylase inhibitor dimethyloxalylglycine attenuated hemin-induced IL-8 secretion. These studies were confirmed via DNA-directed siRNA silencing of HIF-1α. In conclusion, hemin induces a serum protein-sensitive pro-inflammatory phenotype in MVEC via an oxidant-sensitive mechanism that is powerfully regulated by HIF-1.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Microvascular Research - Volume 73, Issue 3, May 2007, Pages 163-172
Journal: Microvascular Research - Volume 73, Issue 3, May 2007, Pages 163-172
نویسندگان
Ramesh Natarajan, Bernard J. Fisher, Alpha A. III,