Light pulse-induced heme and iron-associated transcripts in mouse brain: a microarray analysis.
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 binding 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 cytochrome 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-regulation of globin gene transcription, thereby releasing iron that in turn controls production of ferritins, and further up-regulating aminolevulinate synthase 2 (Alas2).
Ben-Shlomo
Rachel
R
Department of Biology, University of Haifa, Israel. ekly@research.haifa.ac.il
Akhtar
Ruth A
RA
Collins
Ben H
BH
Judah
David J
DJ
Davies
Reginald
R
Kyriacou
Charalambos P
CP
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D002248:Carbon Monoxide / Q000378:metabolism; D016000:Cluster Analysis; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006418:Heme / Q000235:genetics / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D006454:Hemoglobins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007501:Iron / Q000378:metabolism*; D008027:Light; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction; D015203:Reproducibility of Results; D014158:Transcription, Genetic
D006454:Hemoglobins; D006418:Heme; D002248:Carbon Monoxide; D007501:Iron; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D009251:NADPH-Ferrihemoprotein Reductase