Heme reversibly damps PERIOD2 rhythms in mouse suprachiasmatic nucleus explants.
Heme reversibly damps PERIOD2 rhythms in mouse suprachiasmatic nucleus explants.
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DOI：
10.1016/j.neuroscience.2009.08.022
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发表时间：
2009-12-01
期刊：
影响因子：
3.3
通讯作者：
Harrington, M. E.
中科院分区：
文献类型：
--
作者：
Guenthner, C. J.;Bickar, D.;Harrington, M. E.
下丘脑视交叉上核(SCN)在哺乳动物中通过同步外周组织中的自主时钟而作为主要的昼夜节律起搏器，由相互连锁的正/负转录/翻译反馈环驱动的单细胞振荡器组成。一些研究表明，血红素是SCN中以昼夜节律方式合成和降解的常见假体基团，可能调节几个反馈回路组件的功能，包括REV-ERB核受体和Perio2(PER2)。我们发现，高铁血红素(氯化血红素，3-100μM)可逆地抑制表达PER2∷荧光素酶(PER2∷Luc)融合蛋白的小鼠的SCN外植体的发光节律，这是剂量依赖的，并且是可逆的。血红素加氧酶(HOS，将血红素降解为胆绿素、一氧化碳和铁)的抑制剂模拟了血红素对PER2节律的影响。相反，抑制血红素和HO对胸腺和食道外植体的发光节律没有影响，对脾组织中PER2∷LUC的抑制作用很小，这表明血红素的作用是组织特异性的。分析了血红素降解产物对SCN、PER2、∷、LUC节律的影响，表明它们可能不是血红素影响节律的原因。血红素合成抑制剂N-甲基原卟啉IX(NMP)使SCN PER2∷LUC节律的昼夜周期延长约1小时。这些数据与血红素在昼夜节律系统中的重要作用是一致的。
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-methylprotoporphyrin IX (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.
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DOI：
10.1523/jneurosci.3801-08.2009
发表时间：
2009-02-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Ciarleglio CM;Gamble KL;Axley JC;Strauss BR;Cohen JY;Colwell CS;McMahon DG
通讯作者：
McMahon DG
影响因子：
4.5
作者：
Liu AC;Tran HG;Zhang EE;Priest AA;Welsh DK;Kay SA
通讯作者：
Kay SA
影响因子：
2.4
作者：
Levine JD;Funes P;Dowse HB;Hall JC
通讯作者：
Hall JC
影响因子：
2.5
作者：
Dwyer BE;Stone ML;Gorman N;Sinclair PR;Perry G;Smith MA;Zhu X
通讯作者：
Zhu X
DOI：
10.1124/jpet.106.102699
发表时间：
2006-10-01
影响因子：
3.5
作者：
Kinobe, Robert T.;Dercho, Ryan A.;Nakatsu, Kanji
通讯作者：
Nakatsu, Kanji