Evaluation of serum sphingolipids and the influence of genetic risk factors in age-related macular degeneration
| Autor: | Pujol-Lereis, Luciana M., Liebisch, Gerhard, Schick, Tina, Lin, Yuchen, Grassmann, Felix, Uchida, Koji, Zipfel, Peter F., Fauser, Sascha, Skerka, Christine, Weber, Bernhard H. F. |
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| Rok vydání: | 2018 |
| Předmět: |
genetic structures
610 Medizin lcsh:Medicine Ciencias de la Salud Gene Expression Biochemistry purl.org/becyt/ford/1 [https] Macular Degeneration Risk Factors Sphingosine N-Acyltransferase Medicine and Health Sciences Macromolecular Structure Analysis Protein Isoforms Geriatric Ophthalmology lcsh:Science Age related macular degeneration Protein Metabolism Aged 80 and over ddc:610 Lipid Analysis Factor H-like protein 1 Retinal Degeneration purl.org/becyt/ford/3.1 [https] Bioquímica y Biología Molecular Middle Aged Sphingolipidomics Lipids Sphingomyelins Medicina Básica Glucosyltransferases Complement Factor H Retinal Disorders purl.org/becyt/ford/3 [https] CIENCIAS NATURALES Y EXACTAS Research Article Cell Physiology CIENCIAS MÉDICAS Y DE LA SALUD Genética Humana Down-Regulation Complement factor H Ceramides Polymorphism Single Nucleotide Cell Line Ciencias Biológicas purl.org/becyt/ford/3.3 [https] Complement C3b Inactivator Proteins Genetics Epidemiología Humans purl.org/becyt/ford/1.6 [https] Molecular Biology Aged Sphingolipids Tumor Suppressor Proteins lcsh:R Genetic Variation Membrane Proteins Biology and Life Sciences Cell Biology Choroidal Neovascularization eye diseases Cell Metabolism Ophthalmology Metabolism Geriatrics Macular Disorders Genetics of Disease lcsh:Q sense organs Y402H variant |
| Zdroj: | PLoS ONE CONICET Digital (CONICET) Consejo Nacional de Investigaciones Científicas y Técnicas instacron:CONICET PLoS ONE, Vol 13, Iss 8, p e0200739 (2018) |
| DOI: | 10.5283/epub.38073 |
| Popis: | Sphingolipids are bioactive molecules associated with oxidative stress, inflammation, and neurodegenerative diseases, but poorly studied in the context of age-related macular degeneration (AMD), a prevalent sight-threatening disease of the ageing retina. Here, we found higher serum levels of hexosylceramide (HexCer) d18:1/16:0 in patients with choroidal neovascularization (CNV) and geographic atrophy (GA), two manifestations of late stage AMD, and higher ceramide (Cer) d18:1/16:0 levels in GA patients. A sensitivity analysis of genetic variants known to be associated with late stage AMD showed that rs1061170 (p.Y402H) in the complement factor H (CFH) gene influences the association of Cer d18:1/ 16:0 with GA. To understand the possible influence of this genetic variant on ceramide levels, we established a cell-based assay to test the modulation of genes in the ceramide metabolism by factor H-like protein 1 (FHL-1), an alternative splicing variant of CFH that also harbors the 402 residue. We first showed that malondialdehyde-acetaldehyde adducts, an oxidation product commonly found in AMD retinas, induces an increase in ceramide levels in WERI-Rb1 cells in accordance with an increased expression of ceramide synthesis genes. Then, we observed that cells exposed to the non-risk FHL-1:Y402, but not the risk associated variant FHL-1:H402 or full-length CFH, downregulated ceramide synthase 2 and ceramide glucosyltransferase gene expression. Together, our findings show that serum ceramide and hexosylceramide species are altered in AMD patients and that ceramide levels may be influenced by AMD associated risk variants. Fil: Pujol Lereis, Luciana Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas. Universidad Católica de Córdoba. Centro de Investigación y Desarrollo en Inmunología y Enfermedades Infecciosas; Argentina Fil: Liebisch, Gerhard. Universitat Regensburg; Alemania Fil: Schick, Tina. Universitat zu Köln; Alemania Fil: Lin, Yuchen. Hans Knöll Institute. Leibniz Institute for Natural Product Research and Infection Biology; Alemania Fil: Grassmann, Felix. Universitat Regensburg; Alemania Fil: Uchida, Koji. No especifica; Argentina Fil: Zipfel, Peter F.. Hans Knöll Institute. Leibniz Institute for Natural Product Research and Infection Biology; Alemania Fil: Fauser, Sascha. Universitat zu Köln; Alemania. Hoffmann-La Roche; Suiza Fil: Skerka, Christine. Hans Knöll Institute. Leibniz Institute for Natural Product Research and Infection Biology; Alemania Fil: Weber, Bernhard H. F.. Universitat Regensburg; Alemania |
| Databáze: | OpenAIRE |
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