Casein kinase 1 gamma integrates oxidative stress and innate immune responses

Animals utilize associated pathways to elicit responses to oxidative stress and infection. The molecular mechanisms coordinating these pathways remain unclear. Here, using C. elegans we identified the highly conserved casein kinase 1 gamma CSNK-1 (also known as CK1g or CSNK1G), as a key regulator of these processes. csnk-1 interacted with the bli-3/tsp-15/doxa-1 dual oxidase genes by nonallelic noncomplementation to negatively regulate animal survival in excess iodide, an oxidative stressor. A conserved interaction was detected between DOXA-1 and CSNK-1 and between their human homologs DUOXA2 and CSNK1G2. csnk-1 deficiency resulted in upregulated expression of innate immunity genes and increased animal survival in the pathogenic Pseudomonas aeruginosa PA14. Phosphoproteomic analyses identified decreased phosphorylation of key innate immunity regulators NSY-1 MAPKKK and LIN-45 Raf in csnk-1(lf) mutants. Indeed, NSY-1 and LIN-45 pathways were required for the increased survival of csnk-1-deficient animals in PA14. Further analyses suggest that CSNK-1 and SKN-1 Nrf2 might act in parallel to regulate oxidative stress response. Together, we propose that CSNK-1 CSNK1G plays a novel pivotal role in integrating animal’s responses to oxidative stress and pathogens.

The Transcriptomic Response of the Murine Thyroid Gland to Iodide Overload and the Role of the Nrf2 Antioxidant System

Background: Thyroid follicular cells have physiologically high levels of reactive oxygen species because oxidation of iodide is essential for the iodination of thyroglobulin (Tg) during thyroid hormone synthesis. Thyroid follicles (the functional units of the thyroid) also utilize incompletely understood autoregulatory mechanisms to defend against exposure to excess iodide. To date, no transcriptomic studies have investigated these phenomena in vivo. Nuclear erythroid factor 2 like 2 (Nrf2 or Nfe2l2) is a transcription factor that regulates the expression of numerous antioxidant and other cytoprotective genes. We showed previously that the Nrf2 pathway regulates the antioxidant defense of follicular cells, as well as Tg transcription and Tg iodination. We, thus, hypothesized that Nrf2 might be involved in the transcriptional response to iodide overload. Methods: C57BL6/J wild-type (WT) or Nrf2 knockout (KO) male mice were administered regular water or water supplemented with 0.05% sodium iodide for seven days. RNA from their thyroids was prepared for next-generation RNA sequencing (RNA-Seq). Gene expression changes were assessed and pathway analyses were performed on the sets of differentially expressed genes. Results: Analysis of differentially expressed messenger RNAs (mRNAs) indicated that iodide overload upregulates inflammatory-, immune-, fibrosis- and oxidative stress-related pathways, including the Nrf2 pathway. Nrf2 KO mice showed a more pronounced inflammatory–autoimmune transcriptional response to iodide than WT mice. Compared to previously published datasets, the response patterns observed in WT mice had strong similarities with the patterns typical of Graves’ disease and papillary thyroid carcinoma (PTC). Long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) also responded to iodide overload, with the latter targeting mRNAs that participate mainly in inflammation pathways. Conclusions: Iodide overload induces the Nrf2 cytoprotective response and upregulates inflammatory, immune, and fibrosis pathways similar to autoimmune hyperthyroidism (Graves’ disease) and PTC.

Surface Interactions and Mechanisms Study on the Removal of Iodide from Water by Use of Natural Zeolite-Based Silver Nanocomposites

In this work a natural zeolite was modified with silver following two different methods to derive Ag2O and Ag0 nanocomposites. The materials were fully characterized and the results showed that both materials were decorated with nanoparticles of size of 5–25 nm. The natural and modified zeolites were used for the removal of iodide from aqueous solutions of initial concentration of 30–1400 ppm. Natural zeolite showed no affinity for iodide while silver forms were very efficient reaching a capacity of up to 132 mg/g. Post-adsorption characterizations showed that AgI was formed on the surface of the modified zeolites and the amount of iodide removed was higher than expected based on the silver content. A combination of experimental data and characterizations indicate that the excess iodide is most probably related to negatively charged AgI colloids and Ag-I complexes forming in the solution as well as on the surface of the modified zeolites.

IODIMETRY-PHOTOMETRIC DETERMINATION OF PERIODATE, IODATE AND BROMATE IN WATER SOLUTIONS

A simple and accurate three-step procedure for sequential spectrophotometric determinations of periodate, iodate and bromate in aqueous media has been developed. At the first stage the determination of periodate is based on the selective oxidation of the excess amount of iodide at pH=4.8 to produce iodine (triiodide), that can be found by spectrophotometric detection (λmax=350 nm). After detecting the analytical signal, iodine is removed from the solution by sorption on the polyurethane foam. In the second stage the determination of iodate is based on the selective oxidation of iodide at pH=3.0 to produce iodine (triiodide), that also can be found by spectrophotometric detection (λmax=350 nm). After detecting the analytical signal, also iodine is removed from the solution by sorption on the polyurethane foam. In the third stage the determination of bromate is based on the selective oxidation of iodide at pH=1.0 to produce iodine (triiodide), that also can be found by spectrophotometric detection (λmax=350 nm). It has been established that the equilibrium in the reaction (ІО4– + 7І– + 8Н+ → 4І2 +4Н2О) is established in 3 minutes at pH=4.8. The equilibrium in the both reactions (ІО3– + 5І– + 6Н+ → 3І2 +3Н2О and BrО3– + 6І– + 6Н+ → 3І2 +Br– +3Н2О) is established in 7 minutes at pH=3.0 and at pH=1.0 respectively. It was found that oxohalogates are quantitatively converted to I2 with ~ 100-fold molar excess iodide at appropriate optimal pH values. Schematically, the determination of IO4–, IO3– and BrO3– in their combined presence can be represented as follows: where SF is spectrophotometry in a solution at 350 nm: PUF is the polyurethane foam. Based on the data obtained, the model mixtures of periodate, iodate and bromate by sequential iodiometry-photometric method were analyzed. The error of determination in mixtures of each oxo-halogenate did not exceed 5%.

Effect of Excess Iodide Intake on Salivary Glands in a Swiss Albino Mice Model

Iodine is an important micronutrient required for nutrition. Excess iodine has adverse effects on thyroid, but there is not enough information regarding its effect on salivary glands. In addition to food and iodized salt, skin disinfectants and maternal nutritional supplements contain iodide, so its intake could be excessive during pregnancy, lactation, and infancy. The aim of this work was to evaluate the effect of excess iodide ingestion on salivary glands during mating, gestation, lactation, and postweaning period in mouse. During assay, mice were allocated into groups: control and treatment groups (received distilled water with NaI 1 mg/mL). Water intake, glandular weight, and histology were analyzed. Treatment groups showed an increase in glandular weight and a significantly (p < 0.05) higher water intake than control groups. Lymphocyte infiltration was observed in animals of treatment groups, while there was no infiltration in glandular sections of control groups. Results demonstrated that a negative relationship could exist between iodide excess and salivary glands. This work is novel evidence that high levels of iodide intake could induce mononuclear infiltration in salivary glands. These results should be considered, especially in pregnant/lactating women, to whom a higher iodine intake is usually recommended.

Effect of iodinated contrast media on thyroid: a brief review

In parallel to the increased use of computed tomography, iodinated contrast agents are increasingly becoming a source of excess iodide. Iodinated contrast agents may induce thyroid dysfunction in exposed patients, especially in the presence of an underlying thyroid disease. Thus, an ordinary dose of the contrast used for the imaging, can induce hyper or hypothyroidism in a patient with subtle thyroid disease. This review will briefly discuss the physiology of iodine and the clinical evaluation of iodine induced thyroid dysfunction.