Role of tyrosine-sulfated proteins in retinal structure and function

Kanan, Yogita; Al‐Ubaidi, Muayyad R.

doi:10.1016/j.exer.2014.07.007

Cited by 4 publications

(2 citation statements)

References 82 publications

(101 reference statements)

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“…For example, tyrosine, which is part of a peptide associated with melanin, neurotransmitters, and hormones, may undergo phosphorylation, sulfation, or nitration and so influence protein function. The mutations in complement factor H, which is a tyrosine-sulfated protein, have been confirmed to affect AMD development [ 27 , 28 ]. Arginine had beneficial effects on endothelial dysfunction for alleviating chronic inflammation of AMD [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma metabolomic study in Chinese patients with wet age-related macular degeneration

et al. 2017

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BackgroundAge-related macular degeneration (AMD) is a leading disease associated with blindness. It has a high incidence and complex pathogenesis. We aimed to study the metabolomic characteristics in Chinese patients with wet AMD by analyzing the morning plasma of 20 healthy controls and 20 wet AMD patients for metabolic differences.MethodsWe used ultra-high-pressure liquid chromatography and quadrupole-time-of-flight mass spectrometry for this analysis. The relationship of these differences with AMD pathophysiology was also assessed. Remaining data were normalized using Pareto scaling, and then valid data were handled using multivariate data analysis with MetaboAnalysis software, including unsupervised principal component analysis and supervised partial least squares-discriminate analysis. The purpose of the present work was to identify significant metabolites for the analyses. Hierarchical clustering was conducted to identify metabolites that differed between the two groups. Significant metabolites were then identified using the established database, and features were mapped on the Kyoto Encyclopedia of Genes and Genomes.ResultsA total of 5443 ion peaks were detected, all of them attributable to the same 10 metabolites. These included some amino acids, isomaltose, hydrocortisone, and biliverdin. The heights of these peaks differed significantly between the two groups. The biosynthesis of amino acids pathways also differed profoundly between patients with wet AMD and controls.ConclusionsThese findings suggested that metabolic profiles and and pathways differed between wet AMD and controls and may provide promising new targets for AMD-directed therapeutics and diagnostics.

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Section: Discussionmentioning

confidence: 99%

Plasma metabolomic study in Chinese patients with wet age-related macular degeneration

et al. 2017

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“…Identifying the relative contributions of renal reabsorption and ileal absorption to maintaining circulating sulfate levels in the pig will be the next phase of our research. The role of SLC13A4 in the eye and choroid plexus is unknown but is most likely to be mediating sulfate supply to the eye and brain for sulfonation of proteoglycans, such as heparan sulfate and chondroitin sulfate which play important roles in maintaining the structure and function of the eye and brain [9] , [32] , [33] . In addition, sulfonation of neurotransmitters and thyroid hormone in the brain contribute to neurological function and neurodevelopment, suggesting a potential role for SLC13A4 in maintaining sulfate homeostasis in the brain [2] , [34] .…”

Section: Resultsmentioning

confidence: 99%

Structure, organization and tissue expression of the pig SLC13A1 and SLC13A4 sulfate transporter genes

Barnes

Eiby

Lee

et al. 2017

Biochemistry and Biophysics Reports

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Sulfate is an obligate nutrient for fetal growth and development. In mice, the renal Slc13a1 sulfate transporter maintains high maternal circulating levels of sulfate in pregnancy, and the placental Slc13a4 sulfate transporter mediates sulfate supply to the fetus. Both of these genes have been linked to severe embryonal defects and fetal loss in mice. However, the clinical significance of SLC13A1 and SLC13A4 in human gestation is unknown. One approach towards understanding the potential involvement of these genes in human fetal pathologies is to use an animal model, such as the pig, which mimics the developmental trajectory of the human fetus more closely than the previously studied mouse models. In this study, we determined the tissue distribution of pig SLC13A1 and SLC13A4 mRNA, and compared the gene, cDNA and protein sequences of the pig, human and mouse homologues. Pig SLC13A1 mRNA was expressed in the ileum and kidney, whereas pig SLC13A4 mRNA was expressed in the placenta, choroid plexus and eye, which is similar to the tissue distribution in human and mouse. The pig SLC13A1 gene contains 15 exons spread over 76 kb on chromosome 8, and encodes a protein of 594 amino acids that shares 90% and 85% identity with the human and mouse homologues, respectively. The pig SLC13A4 gene is located approximately 11 Mb from SLC13A1 on chromosome 8, and contains 16 exons spanning approximately 70 kb. The pig SLC13A4 protein contains 626 amino acids that share 91% and 90% identity with human and mouse homologues, respectively. The 5’-flanking region of SLC13A1 contains several putative transcription factor binding sites, including GATA-1, GATA-3, Oct1 and TATA-box consensus sequences, which are conserved in the homologous human and mouse sequences. The 5’-flanking sequence of SLC13A4 contains multiple putative transcription factor consensus sites, including GATA-1, TATA-box and Vitamin D responsive elements. This is the first report to define the tissue distribution of pig SLC13A1 and SLC13A4 mRNAs, and compare the gene, cDNA, 5’-flanking region and protein sequences to human and mouse.

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