Alpha-crystallin mutations alter lens metabolites in mouse models of human cataracts
| Autor: | Usha P. Andley, Stephanie L. Bozeman, Fong-Fu Hsu, Cheryl Frankfater |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | PLoS ONE PLoS ONE, Vol 15, Iss 8, p e0238081 (2020) |
| ISSN: | 1932-6203 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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