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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 1755-375X ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23742627 Approved no  
  Call Number IDA @ john @ Serial 346  
Permanent link to this record
 

 
Author van Diepen, H.C.; Foster, R.G.; Meijer, J.H. url  doi
openurl 
  Title A colourful clock Type Journal Article
  Year 2015 Publication 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. 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  
  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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