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Author van der Burght, B.W.; Hansen, M.; Olsen, J.; Zhou, J.; Wu, Y.; Nissen, M.H.; Sparrow, J.R. url  doi
openurl 
  Title Early changes in gene expression induced by blue light irradiation of A2E-laden retinal pigment epithelial cells Type Journal Article
  Year 2013 Publication Acta Ophthalmologica Abbreviated Journal Acta Ophthalmol  
  Volume 91 Issue 7 Pages e537-45  
  Keywords Apoptosis; Cell Line; Cell Survival; Gene Expression Regulation/*physiology; Humans; Light; Lipofuscin/genetics; Oligonucleotide Array Sequence Analysis; Principal Component Analysis; Pyridinium Compounds; RNA, Messenger/genetics; Real-Time Polymerase Chain Reaction; Retinal Pigment Epithelium/metabolism/pathology/*radiation effects; Retinoids/*genetics; Transcriptome; A2e; age-related macular degeneration; apoptosis; complement cascade; gene expression; retinal pigment epithelial cells; blue light; retinal pigment epithelial; epigenetics  
  Abstract PURPOSE: Accumulation of bisretinoids as lipofuscin in retinal pigment epithelial (RPE) cells is implicated in the pathogenesis of some blinding diseases including age-related macular degeneration (AMD). To identify genes whose expression may change under conditions of bisretinoid accumulation, we investigated the differential gene expression in RPE cells that had accumulated the lipofuscin fluorophore A2E and were exposed to blue light (430 nm). METHODS: A2E-laden RPE cells were exposed to blue light (A2E/430 nm) at various time intervals. Cell death was quantified using Dead Red staining, and RNA levels for the entire genome was determined using DNA microarrays (Affymetrix GeneChip Human Genome 2.0 Plus). Array results for selected genes were confirmed by real-time reverse-transcriptase polymerase chain reaction. RESULTS: Principal component analysis revealed that the A2E-laden RPE cells irradiated with blue light were clearly distinguishable from the control samples. We found differential regulation of genes belonging to the following functional groups: transcription factors, stress response, apoptosis and immune response. Among the last mentioned were downregulation of four genes that coded for proteins that have an inhibitory effect on the complement cascade: (complement factor H, complement factor H-related 1, complement factor I and vitronectin) and of two belonging to the classical pathway (complement component 1, s subcomponent and complement component 1, r subcomponent). CONCLUSION: This study demonstrates that blue light irradiation of A2E-laden RPE cells can alter the transcription of genes belonging to different functional pathways including stress response, apoptosis and the immune response. We suggest that these molecules may be associated to the pathogenesis of AMD and can potentially serve as future therapeutic targets.  
  Address Department of International Health, Immunology and Microbiology, Eye Research Unit, University of Copenhagen, Copenhagen, DenmarkDepartment of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen, DenmarkDepartment of Ophthalmology, Columbia University, New York, New York, 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 (up) 1755-375X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23742627 Approved no  
  Call Number IDA @ john @ Serial 346  
Permanent link to this record
 

 
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. url  doi
openurl 
  Title Circadian disruption accelerates tumor growth and angio/stromagenesis through a Wnt signaling pathway Type Journal Article
  Year 2010 Publication 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  
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  Language English Summary Language Original Title  
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  ISSN (up) 1932-6203 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:21203463; PMCID:PMC3009728 Approved no  
  Call Number IDA @ john @ Serial 162  
Permanent link to this record
 

 
Author Gooley, J.J.; Rajaratnam, S.M.W.; Brainard, G.C.; Kronauer, R.E.; Czeisler, C.A.; Lockley, S.W. url  doi
openurl 
  Title Spectral responses of the human circadian system depend on the irradiance and duration of exposure to light Type Journal Article
  Year 2010 Publication 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  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN (up) 1946-6234 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:20463367 Approved no  
  Call Number IDA @ john @ Serial 294  
Permanent link to this record
 

 
Author Hong, F.; Pan, S.; Xu, P.; Xue, T.; Wang, J.; Guo, Y.; Jia, L.; Qiao, X.; Li, L.; Zhai, Y. url  doi
openurl 
  Title Melatonin Orchestrates Lipid Homeostasis through the Hepatointestinal Circadian Clock and Microbiota during Constant Light Exposure Type Journal Article
  Year 2020 Publication Cells Abbreviated Journal Cells  
  Volume 9 Issue 2 Pages in press  
  Keywords Animals; Cells; Lan; hepatointestinal; lipid homeostasis; melatonin; microbiota  
  Abstract Misalignment between natural light rhythm and modern life activities induces disruption of the circadian rhythm. It is mainly evident that light at night (LAN) interferes with the human endocrine system and contributes to the increasing rates of obesity and lipid metabolic disease. Maintaining hepatointestinal circadian homeostasis is vital for improving lipid homeostasis. Melatonin is a chronobiotic substance that plays a main role in stabilizing bodily rhythm and has shown beneficial effects in protecting against obesity. Based on the dual effect of circadian rhythm regulation and antiobesity, we tested the effect of melatonin in mice under constant light exposure. Exposure to 24-h constant light (LL) increased weight and insulin resistance compared with those of the control group (12-h light-12-h dark cycle, LD), and simultaneous supplementation in the melatonin group (LLM) ameliorated this phenotype. Constant light exposure disturbed the expression pattern of a series of transcripts, including lipid metabolism, circadian regulation and nuclear receptors in the liver. Melatonin also showed beneficial effects in improving lipid metabolism and circadian rhythm homeostasis. Furthermore, the LL group had increased absorption and digestion of lipids in the intestine as evidenced by the elevated influx of lipids in the duodenum and decrease in the efflux of lipids in the jejunum. More interestingly, melatonin ameliorated the gut microbiota dysbiosis and improved lipid efflux from the intestine. Thus, these findings offer a novel clue regarding the obesity-promoting effect attributed to LAN and suggest a possibility for obesity therapy by melatonin in which melatonin could ameliorate rhythm disorder and intestinal dysbiosis.  
  Address Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing 100875, China  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
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  ISSN (up) 2073-4409 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:32093272 Approved no  
  Call Number GFZ @ kyba @ Serial 2854  
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