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Author van Diepen, H.C.; Foster, R.G.; Meijer, J.H.
Title A colourful clock Type Journal Article
Year 2015 Publication (up) PLoS Biology Abbreviated Journal PLoS Biol
Volume 13 Issue 5 Pages e1002160
Keywords Animals; Commentary; *Circadian Rhythm; suprachiasmatic nuclei; melanopsin; retinal ganglion cells; entrainment; photoperiod
Abstract Circadian rhythms are an essential property of life on Earth. In mammals, these rhythms are coordinated by a small set of neurons, located in the suprachiasmatic nuclei (SCN). The environmental light/dark cycle synchronizes (entrains) the SCN via a distinct pathway, originating in a subset of photosensitive retinal ganglion cells (pRGCs) that utilize the photopigment melanopsin (OPN4). The pRGCs are also innervated by rods and cones and, so, are both endogenously and exogenously light sensitive. Accumulating evidence has shown that the circadian system is sensitive to ultraviolet (UV), blue, and green wavelengths of light. However, it was unclear whether colour perception itself can help entrain the SCN. By utilizing both behavioural and electrophysiological recording techniques, Walmsley and colleagues show that multiple photic channels interact and enhance the capacity of the SCN to synchronize to the environmental cycle. Thus, entrainment of the circadian system combines both environmental irradiance and colour information to ensure that internal and external time are appropriately aligned.
Address Laboratory for Neurophysiology, Department of Molecular Cell Biology, Leiden University medical School, Leiden, The Netherlands
Corporate Author Thesis
Publisher PLOS Place of Publication Editor
Language English Summary Language English Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1544-9173 ISBN Medium
Area Expedition Conference
Notes PMID:25996907; PMCID:PMC4440787 Approved no
Call Number LoNNe @ christopher.kyba @ Serial 1183
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Author Yasuniwa, Y.; Izumi, H.; Wang, K.-Y.; Shimajiri, S.; Sasaguri, Y.; Kawai, K.; Kasai, H.; Shimada, T.; Miyake, K.; Kashiwagi, E.; Hirano, G.; Kidani, A.; Akiyama, M.; Han, B.; Wu, Y.; Ieiri, I.; Higuchi, S.; Kohno, K.
Title Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway Type Journal Article
Year 2010 Publication (up) PloS one Abbreviated Journal PLoS One
Volume 5 Issue 12 Pages e15330
Keywords Animals; *Circadian Rhythm; Disease Progression; *Gene Expression Regulation, Neoplastic; HeLa Cells; Humans; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Neoplasm Transplantation; Neoplasms/*pathology; *Neovascularization, Pathologic; Nerve Tissue Proteins/metabolism; Skin/metabolism; Vascular Endothelial Growth Factor A/metabolism; Wnt Proteins/*metabolism; Oncogenesis
Abstract Epidemiologic studies show a high incidence of cancer in shift workers, suggesting a possible relationship between circadian rhythms and tumorigenesis. However, the precise molecular mechanism played by circadian rhythms in tumor progression is not known. To identify the possible mechanisms underlying tumor progression related to circadian rhythms, we set up nude mouse xenograft models. HeLa cells were injected in nude mice and nude mice were moved to two different cases, one case is exposed to a 24-hour light cycle (L/L), the other is a more “normal” 12-hour light/dark cycle (L/D). We found a significant increase in tumor volume in the L/L group compared with the L/D group. In addition, tumor microvessels and stroma were strongly increased in L/L mice. Although there was a hypervascularization in L/L tumors, there was no associated increase in the production of vascular endothelial cell growth factor (VEGF). DNA microarray analysis showed enhanced expression of WNT10A, and our subsequent study revealed that WNT10A stimulates the growth of both microvascular endothelial cells and fibroblasts in tumors from light-stressed mice, along with marked increases in angio/stromagenesis. Only the tumor stroma stained positive for WNT10A and WNT10A is also highly expressed in keloid dermal fibroblasts but not in normal dermal fibroblasts indicated that WNT10A may be a novel angio/stromagenic growth factor. These findings suggest that circadian disruption induces the progression of malignant tumors via a Wnt signaling pathway.
Address Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1932-6203 ISBN Medium
Area Expedition Conference
Notes PMID:21203463; PMCID:PMC3009728 Approved no
Call Number IDA @ john @ Serial 162
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Author Sporl, F.; Korge, S.; Jurchott, K.; Wunderskirchner, M.; Schellenberg, K.; Heins, S.; Specht, A.; Stoll, C.; Klemz, R.; Maier, B.; Wenck, H.; Schrader, A.; Kunz, D.; Blatt, T.; Kramer, A.
Title Kruppel-like factor 9 is a circadian transcription factor in human epidermis that controls proliferation of keratinocytes Type Journal Article
Year 2012 Publication (up) Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A
Volume 109 Issue 27 Pages 10903-10908
Keywords Human Health; Anti-Inflammatory Agents/pharmacology; Biological Clocks/genetics/physiology; Cell Differentiation/physiology; Cell Proliferation/drug effects; Cells, Cultured; Circadian Rhythm/genetics/*physiology; Epidermis/cytology/*physiology; Genome-Wide Association Study; Homeostasis/physiology; Humans; Hydrocortisone/pharmacology; Keratinocytes/cytology/drug effects/*physiology; Kruppel-Like Transcription Factors/*genetics/*metabolism; Luciferases/genetics; Skin Neoplasms/genetics/physiopathology
Abstract Circadian clocks govern a wide range of cellular and physiological functions in various organisms. Recent evidence suggests distinct functions of local clocks in peripheral mammalian tissues such as immune responses and cell cycle control. However, studying circadian action in peripheral tissues has been limited so far to mouse models, leaving the implication for human systems widely elusive. In particular, circadian rhythms in human skin, which is naturally exposed to strong daytime-dependent changes in the environment, have not been investigated to date on a molecular level. Here, we present a comprehensive analysis of circadian gene expression in human epidermis. Whole-genome microarray analysis of suction-blister epidermis obtained throughout the day revealed a functional circadian clock in epidermal keratinocytes with hundreds of transcripts regulated in a daytime-dependent manner. Among those, we identified a circadian transcription factor, Kruppel-like factor 9 (Klf9), that is substantially up-regulated in a cortisol and differentiation-state-dependent manner. Gain- and loss-of-function experiments showed strong antiproliferative effects of Klf9. Putative Klf9 target genes include proliferation/differentiation markers that also show circadian expression in vivo, suggesting that Klf9 affects keratinocyte proliferation/differentiation by controlling the expression of target genes in a daytime-dependent manner.
Address Research and Development, Beiersdorf AG, 20245 Hamburg, Germany
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0027-8424 ISBN Medium
Area Expedition Conference
Notes PMID:22711835; PMCID:PMC3390879 Approved no
Call Number LoNNe @ kagoburian @ Serial 814
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Author Berson, D.M.; Dunn, F.A.; Takao, M.
Title Phototransduction by retinal ganglion cells that set the circadian clock Type Journal Article
Year 2002 Publication (up) Science (New York, N.Y.) Abbreviated Journal Science
Volume 295 Issue 5557 Pages 1070-1073
Keywords Human Health; Animals; Axons/ultrastructure; *Biological Clocks; *Circadian Rhythm; Dendrites/ultrastructure; Isoquinolines; Kinetics; Light; *Light Signal Transduction; Patch-Clamp Techniques; Rats; Rats, Sprague-Dawley; Retinal Ganglion Cells/chemistry/cytology/*physiology; Rod Opsins/analysis/physiology; Suprachiasmatic Nucleus/cytology/*physiology
Abstract Light synchronizes mammalian circadian rhythms with environmental time by modulating retinal input to the circadian pacemaker-the suprachiasmatic nucleus (SCN) of the hypothalamus. Such photic entrainment requires neither rods nor cones, the only known retinal photoreceptors. Here, we show that retinal ganglion cells innervating the SCN are intrinsically photosensitive. Unlike other ganglion cells, they depolarized in response to light even when all synaptic input from rods and cones was blocked. The sensitivity, spectral tuning, and slow kinetics of this light response matched those of the photic entrainment mechanism, suggesting that these ganglion cells may be the primary photoreceptors for this system.
Address Department of Neuroscience, Brown University, Providence, RI, 02912 USA. David_Berson@brown.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0036-8075 ISBN Medium
Area Expedition Conference
Notes PMID:11834835 Approved no
Call Number LoNNe @ kagoburian @ Serial 720
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Author Gooley, J.J.; Rajaratnam, S.M.W.; Brainard, G.C.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W.
Title Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light Type Journal Article
Year 2010 Publication (up) Science Translational Medicine Abbreviated Journal Sci Transl Med
Volume 2 Issue 31 Pages 31ra33
Keywords Adolescent; Adult; Circadian Rhythm/physiology/*radiation effects; Dose-Response Relationship, Radiation; Humans; Light; Melatonin/secretion; Photoperiod; Phototherapy; Retina/physiology/radiation effects; Retinal Cone Photoreceptor Cells/physiology/radiation effects; Retinal Ganglion Cells/physiology/radiation effects; Rod Opsins/physiology; Young Adult; blue light; light at night; melatonin; melanopsin; light therapy
Abstract In humans, modulation of circadian rhythms by light is thought to be mediated primarily by melanopsin-containing retinal ganglion cells, not rods or cones. Melanopsin cells are intrinsically blue light-sensitive but also receive input from visual photoreceptors. We therefore tested in humans whether cone photoreceptors contribute to the regulation of circadian and neuroendocrine light responses. Dose-response curves for melatonin suppression and circadian phase resetting were constructed in subjects exposed to blue (460 nm) or green (555 nm) light near the onset of nocturnal melatonin secretion. At the beginning of the intervention, 555-nm light was equally effective as 460-nm light at suppressing melatonin, suggesting a significant contribution from the three-cone visual system (lambda(max) = 555 nm). During the light exposure, however, the spectral sensitivity to 555-nm light decayed exponentially relative to 460-nm light. For phase-resetting responses, the effects of exposure to low-irradiance 555-nm light were too large relative to 460-nm light to be explained solely by the activation of melanopsin. Our findings suggest that cone photoreceptors contribute substantially to nonvisual responses at the beginning of a light exposure and at low irradiances, whereas melanopsin appears to be the primary circadian photopigment in response to long-duration light exposure and at high irradiances. These results suggest that light therapy for sleep disorders and other indications might be optimized by stimulating both photoreceptor systems.
Address Division of Sleep Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1946-6234 ISBN Medium
Area Expedition Conference
Notes PMID:20463367 Approved no
Call Number IDA @ john @ Serial 294
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