Document Type
Article
Publication Date
12-1-2009
Publication Title
Neuroscience
Abstract
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.
Keywords
circadian, clock genes, desynchronization, luciferase, NR1D1, tissue culture
Volume
164
Issue
2
First Page
832
Last Page
841
DOI
10.1016/j.neuroscience.2009.08.022
ISSN
03064522
Recommended Citation
Guenthner, C. J.; Bickar, David; and Harrington, Mary E., "Heme Reversibly Damps PERIOD2 Rhythms in Mouse Suprachiasmatic Nucleus Explants" (2009). Psychology: Faculty Publications, Smith College, Northampton, MA.
https://scholarworks.smith.edu/psy_facpubs/96
Comments
Peer reviewed accepted manuscript.