Iodotyrosines are biomarkers for preclinical stages of iodine-deficient hypothyroidism in Dehal1 knockout mice

BACKGROUND: Iodine is required for the synthesis of thyroid hormone (TH), but its natural availability is limited. Dehalogenase1 (Dehal1) recycles iodine from mono- and di-iodotyrosines (MIT, DIT) to sustain TH synthesis when iodine supplies are scarce, but its role in the dynamics of storage and conservation of iodine is unknown. METHODS: Dehal1 knockout mice (Dehal1KO) were generated by gene-trapping and the timing of expression and distribution was investigated by X-Gal staining and immunofluorescence using recombinant Dehal1-Betagalactosidase protein produced in fetuses and adult mice. Adult Dehal1KO and wild-type (Wt) animals were fed normal and iodine-deficient diets for 1 month and plasma, urine, and tissues were isolated for analyses. TH status was monitored including T4, T3, MIT, DIT, and urinary iodine concentration using a novel LC-MS-MS method and the Sandell-Kolthoff (S-K) technique throughout the experimental period. RESULTS: Dehal1 is highly expressed in the thyroid, is also present in kidneys, liver, and, unexpectedly, the choroid plexus. In vivo transcription of Dehal1 was induced by iodine deficiency only in the thyroid tissue. Under normal iodine intake, Dehal1KO mice were euthyroid but they showed negative iodine balance due to a continuous loss of iodotyrosines in the urine. Counter-intuitively, the urinary iodine concentration of Dehal1KO mice is two-fold higher than in Wt mice, indicating S-K measures both inorganic and organic iodine. Under iodine restriction, Dehal1KO mice rapidly develop profound hypothyroidism while Wt mice remain euthyroid, suggesting reduced retention of iodine in Dehal1KO mice. Urinary and plasma iodotyrosines were continually elevated throughout their life cycle, including the neonatal period, when pups are still euthyroid. CONCLUSIONS: Plasma and urine iodotyrosine elevation occurs in Dehal1-deficient mice throughout life. Therefore, measurement of iodotyrosines predicts an eventual iodine shortage and development of hypothyroidism in the pre-clinical phase. The prompt establishment of hypothyroidism upon the start of iodine restriction suggests that Dehal1KO mice have low iodine reserves in their thyroid glands, pointing to defective capacity for iodine storage

PlantPReS : a database for plant proteome response to stress

About 75% of plant yield potential has been estimated to be lost to environmental stresses, even in developed agricultures. To facilitate the biotechnological improvement of crop productivity, genes and proteins that control crop adaptation to a wide range of environments will need to be identified. Due to the challenges faced in text/data mining, there is a large gap between the data available to researchers and the hundreds of published plant stress proteomics articles. Plant stress proteome database (PlantPReS; www.proteome.ir) is an open online proteomic database, which currently (as of October 2015) comprises >20,413 entries from 456 manually curated articles, and contains >10,600 unique stress responsive proteins. Since every aspect of the experiments, including protein name, accession number, plant type, tissue, stress types, organelles, and developmental stage has been digitized, experimental data can be rapidly accessed and integrated. Furthermore, PlantPReS enables researchers to perform multiple analyses on the database using the filtration mode, and the results of each query indicate a series of proteins for which a set of selected criteria is met. The query results can be displayed in either text or graphical format. Significance: The promise of text and data mining to facilitate and enhance research fundamentally has not yet been achieved, mainly because great numbers of stress-associated proteins are not deposited in databases. PlantPReS is a valuable database for the vast majority of researchers working in proteomics and plant stress areas. It has a user-friendly interface with a number of useful features, including a search engine, analysis tools, gene ontology, a function for cross-referencing useful external databases, and the expression pattern of stress associated proteins.4 page(s