کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
4339830 | 1295768 | 2009 | 10 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Heme reversibly damps PERIOD2 rhythms in mouse suprachiasmatic nucleus explants
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کلمات کلیدی
LPSNR1D1NMPTLR4PPIXSCNROSs - ROS هاSnPP - SNPPtumor necrosis factor α - تومور نکروز عامل αcircadian - دیروزTNF-α - فاکتور نکروز توموری آلفاluciferase - لوسیفرازlipopolysaccharide - لیپوپلی ساکاریدcarbon monoxide - منوکسیدکربنDesynchronization - نرمافزارSuprachiasmatic nucleus - هستههای سوپراکیاسماتیکheme oxygenase - همگام اکسژنازprotoporphyrin IX - پروتوپورفیرین IXtin protoporphyrin IX - پروتوپورفیرین IXClock genes - ژنهای ساعتTissue culture - کشت بافتReactive oxygen species - گونههای فعال اکسیژنToll-like receptor 4 - گیرنده تله مانند 4
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
The hypothalamic suprachiasmatic nucleus (SCN), which in mammals serves as the master circadian pacemaker by synchronizing autonomous clocks in peripheral tissues, is composed of coupled single-cell oscillators that are driven by interlocking positive/negative transcriptional/translational feedback loops. Several studies have suggested that heme, a common prosthetic group that is synthesized and degraded in a circadian manner in the SCN, may modulate the function of several feedback loop components, including the REV-ERB nuclear receptors and PERIOD2 (PER2). We found that ferric heme (hemin, 3-100 μM) dose-dependently and reversibly damped luminescence rhythms in SCN explants from mice expressing a PER2::LUCIFERASE (PER2::LUC) fusion protein. Inhibitors of heme oxygenases (HOs, which degrade heme to biliverdin, carbon monoxide, and iron) mimicked heme's effects on PER2 rhythms. In contrast, heme and HO inhibition did not damp luminescence rhythms in thymus and esophagus explants and had only a small effect on PER2::LUC damping in spleen explants, suggesting that heme's effects are tissue-specific. Analysis of the effects of heme's degradation products on SCN PER2::LUC rhythms indicated that they probably were not responsible for heme's effects on rhythms. The heme synthesis inhibitor N-methylprotoporphyrinIX (NMP) lengthened the circadian period of SCN PER2::LUC rhythms by about an hour. These data are consistent with an important role for heme in the circadian system.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience - Volume 164, Issue 2, 1 December 2009, Pages 832-841
Journal: Neuroscience - Volume 164, Issue 2, 1 December 2009, Pages 832-841
نویسندگان
C.J. Guenthner, D. Bickar, M.E. Harrington,