Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts
| العنوان: | Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts |
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| المؤلفون: | Usha P. Andley, Stephanie L. Bozeman, Fong-Fu Hsu, Cheryl Frankfater |
| المصدر: | PLoS ONE PLoS ONE, Vol 15, Iss 8, p e0238081 (2020) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, genetic structures, Eye Diseases, Biochemistry, Mass Spectrometry, Analytical Chemistry, Lens protein, Mice, 0302 clinical medicine, Medical Conditions, Spectrum Analysis Techniques, Aspartic acid, Medicine and Health Sciences, Metabolites, alpha-Crystallins, Protein Metabolism, chemistry.chemical_classification, Multidisciplinary, Eye Lens, Chromatographic Techniques, Animal Models, Lipids, Amino acid, Sterols, Chemistry, Cholesterol, Experimental Organism Systems, Physical Sciences, Medicine, Leucine, Anatomy, Research Article, Science, Ocular Anatomy, Mouse Models, Research and Analysis Methods, Gas Chromatography-Mass Spectrometry, Cataract, 03 medical and health sciences, Model Organisms, Cataracts, Valine, Crystallin, Ocular System, Lens, Crystalline, medicine, Animals, Humans, Metabolomics, Biology and Life Sciences, Correction, medicine.disease, eye diseases, Mice, Inbred C57BL, Ophthalmology, Disease Models, Animal, 030104 developmental biology, Metabolism, chemistry, Lens Disorders, Mutation, 030221 ophthalmology & optometry, Animal Studies, sense organs, Isoleucine |
| الوصف: | Cataracts are a major cause of blindness worldwide and commonly occur in individuals over 70 years old. Cataracts can also appear earlier in life due to genetic mutations. The lens proteins, αA- and αB-crystallins, are chaperone proteins that have important roles maintaining protein solubility to prevent cataract formation. Mutations in the CRYAA and CRYAB crystallin genes are associated with autosomal dominant early onset human cataracts. Although studies about the proteomic and genomic changes that occur in cataracts have been reported, metabolomics studies are very limited. Here, we directly investigated cataract metabolism using gas-chromatography-mass spectrometry (GC-MS) to analyze the metabolites in adult Cryaa-R49C and Cryab-R120G knock-in mouse lenses. The most abundant metabolites were myo-inositol, L-(+)-lactic acid, cholesterol, phosphate, glycerol phosphate, palmitic and 9-octadecenoic acids, α-D-mannopyranose, and β-D-glucopyranose. Cryaa-R49C knock-in mouse lenses had a significant decrease in the number of sugars and minor sterols, which occurred in concert with an increase in lactic acid. Cholesterol composition was unchanged. In contrast, Cryab-R120G knock-in lenses exhibited increased total amino acid content including valine, alanine, serine, leucine, isoleucine, glycine, and aspartic acid. Minor sterols, including cholest-7-en-3-ol and glycerol phosphate were decreased. These studies indicate that lenses from Cryaa-R49C and Cryab-R120G knock-in mice, which are models for human cataracts, have unique amino acid and metabolite profiles. |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8ef0b801b36931242f770ac84eca79e4Test https://pubmed.ncbi.nlm.nih.gov/33216808Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8ef0b801b36931242f770ac84eca79e4 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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