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Light pulse-induced heme and iron-associated transcripts in mouse brain: a microarray analysis

Ben-Shlomo, Rachel; Akhtar, Ruth A.; Collins, Ben H.; Judah, David J.; Davies, Reginald and Kyriacou, Charalambos P. (2005). Light pulse-induced heme and iron-associated transcripts in mouse brain: a microarray analysis. Chronobiology International, 22(3) pp. 455–471.

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Synchronization of circadian oscillators With the Outside world is achieved by the acute effects of light on the levels of one or more clock components. In mammals the PAS transcription factors Clock, NPAS2, and BMAL1 regulate gene expression as a function of the day-night cycle. Both PAS domains of NPAS2 were found to bind heme as a prosthetic group, form a gas-regulated sensor, and exert heme-status control of DNA bin ding in vitro. In a microarray analysis comparing overall changes in brain transcript levels between mice subjected to light pulses during the dark phase with animals maintained in darkness, we traced consistent changes in more than 200 different transcripts. Of these, 20 are associated with heme and iron biosynthesis and catabolism. A model for the pathway of induction of heme and iron homeostasis-related transcripts resulting from light pulses Suggests that light signals (as stressors) induce transcription of heme oxygenase 2 (Hmox2) and cyochrome P450 oxidoreductase (Por), which may serve as a primary line of cellular defense. HMOX2 degrades heme from proteins such as hemoglobin. This degradation generates CO, a signal molecule, and may also change the redox state of the cell by reducing the NADPH/NADP ratio. This could lead to up-regulafion of globin gene transcription, thereby releasing iron that in turn controls production of ferritins, and further up-regulating aminolevulinale synthase 2 (Alas2).

Item Type: Journal Item
Copyright Holders: 2005 Taylor & Francis, Inc.
ISSN: 0742-0528
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetBBSRC (Biotechnology and Biological Sciences Research Council)
Keywords: heme and iron metabolism; circadian rhythm; light pulses; molecular mechanism of entrainment; biological clocks
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Item ID: 18179
Depositing User: Colin Smith
Date Deposited: 11 Sep 2009 15:32
Last Modified: 04 Oct 2016 10:27
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