کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5913455 | 1162421 | 2014 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
A chemical screen identifies small molecules that regulate hepcidin expression
ترجمه فارسی عنوان
یک صفحه شیمیایی، مولکول های کوچک را تنظیم می کند که بیانگر هپسیدین است
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شناسی مولکولی
چکیده انگلیسی
Hepcidin, a peptide hormone produced in the liver, decreases intestinal iron absorption and macrophage iron release via effects on ferroportin. Bone morphogenic protein and Stat3 signaling regulate Hepcidin's transcription. Hepcidin is a potential drug target for patients with iron overload syndromes because its levels are inappropriately low in these individuals. To generate a tool for identifying small molecules that modulate Hepcidin expression, we stably transfected human hepatocytes (HepG2) cells with a reporter construct containing 2.7Â kb of the human Hepcidin promoter upstream of a firefly reporter gene. We used high throughput methods to screen 10,169 chemicals in duplicate for their effect on Hepcidin expression and cell viability. Regulators were identified as chemicals that caused a change >Â 3 standard deviations above or >Â 1 standard deviation below the mean of the other chemicals (z-score >Â 3 or <Â 1), while not adversely affecting cell viability, quantified by fluorescence assay. Following validation assays, we identified 16 chemicals in a broad range of functional classes that promote Hepcidin expression. All of the chemicals identified increased expression of bone morphogenic protein-dependent and/or Stat3-dependent genes, however none of them strongly increased phosphorylation of Smad1,5,8 or Stat3.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Blood Cells, Molecules, and Diseases - Volume 53, Issue 4, December 2014, Pages 231-240
Journal: Blood Cells, Molecules, and Diseases - Volume 53, Issue 4, December 2014, Pages 231-240
نویسندگان
Vera Gaun, Bonnie Patchen, Josephine Volovetz, Aileen W. Zhen, Aleksandr Andreev, Michael P. Pollastri, Paula G. Fraenkel,