This study analyzes the uptake and antiproliferative effect of two different chemical forms of iodine, iodide (I K ) and molecular iodine (I 2 ), in MCF-7 cells, which are inducible for the Na C =I K symporter (NIS) and positive for pendrin (PDS). The mouse fibroblast cell line NIH3T3 was used as control. Our results show that in MCF-7 cells, IK uptake is sustained and dependent on NIS, whereas I 2 uptake is transient with a maximal peak at 10 min and a final retention of 10% of total uptake. In contrast, no I K was taken up by NIH3T3 cells, and although I 2 was captured with the same time pattern as in MCF-7 cells, its uptake was significantly lower, and it was not retained within the cell. The uptake of I 2 is independent of NIS, PDS, Na C , and energy, but it is saturable and dependent on protein synthesis, suggesting a facilitated diffusion system. Radioiodine was incorporated into protein and lipid fractions only with I 2 treatment. The administration of non-radiolabeled I 2 and 6-iodo-5-hydroxy-8,11,14-eicosatrienoic acid (6-iodolactone, an iodinated arachidonic acid), but not KI, significantly inhibited proliferation of MCF-7 cells. Proliferation of NIH3T3 cells was not inhibited by 20 mM I 2 . In conclusion, these results demonstrate that I 2 uptake does not depend on NIS or PDS; they suggest that in mammary cancer cells, I 2 is taken up by a facilitated diffusion system and then covalently bound to lipids or proteins that, in turn, inhibit proliferation.

Previous reports have documented the antiproliferative properties of I 2 and the arachidonic acid (AA) derivative 6-iodolactone (6-IL) in both thyroid and mammary glands. In this study, we characterized the cellular pathways activated by these molecules and their effects on cell cycle arrest and apoptosis in normal (MCF-12F) and cancerous (MCF-7) breast cells. Low-to-moderate concentrations of I 2 (10-20 mM) cause G1 and G2/M phase arrest in MCF-12F and caspase-dependent apoptosis in MCF-7 cells. In normal cells, only high doses of I 2 (40 mM) induced apoptosis, and this effect was mediated by poly (ADP-ribose) polymerase-1 (PARP1) and the apoptosis-induced factor, suggesting an oxidative influence of iodine at high concentrations. Our data indicate that both I 2 and 6-IL trigger the same intracellular pathways and suggest that the antineoplasic effect of I 2 in mammary cancer involves the intracellular formation of 6-IL. Mammary cancer cells are known to contain high concentrations of AA, which might explain why I 2 exerts apoptotic effects at lower concentrations only in tumoral cells.

Introduction: Studies in mammary cancer demonstrated that moderately high concentrations of molecular iodine (I 2 ) have a antiproliferative and apoptotic effect either in vivo as in vitro, however the cellular intermediated involved in these effects has not been elucidated.

Candida glabrata, a common opportunistic fungal pathogen, adheres efficiently to mammalian epithelial cells in culture. This interaction in vitro depends mainly on the adhesin Epa1, one of a large family of cell wall proteins. Most of the EPA genes are located in subtelomeric regions, where they are transcriptionally repressed by silencing. In order to better characterize the transcriptional regulation of the EPA family, we have assessed the importance of C. glabrata orthologues of known regulators of subtelomeric silencing in Saccharomyces cerevisiae. To this end, we used a series of strains containing insertions of the reporter URA3 gene within different intergenic regions throughout four telomeres of C. glabrata. Using these reporter strains, we have assessed the roles of SIR2, SIR3, SIR4, HDF1 (yKu70), HDF2 (yKu80), and RIF1 in mediating silencing at four C. glabrata telomeres. We found that, whereas the SIR proteins are absolutely required for silencing of the reporter genes and the native subtelomeric EPA genes, the Rif1 and the Ku proteins regulate silencing at only a subset of the analyzed telomeres. We also mapped a cis element adjacent to the EPA3 locus that can silence a reporter gene when placed at a distance of 31 kb from the telomere. Our data show that silencing of the C. glabrata telomeres varies from telomere to telomere. In addition, recruitment of silencing proteins to the subtelomeres is likely, for certain telomeres, to depend both on the telomeric repeats and on particular discrete silencing elements.

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Background: Previously has been reported the antioxidant function of iodine, and iodine deficiency as a risk factor of preeclampsia.Aim: We analyze the association between iodine deficiency, oxidative stress and antioxidant status with hypertensive disease of pregnancy (HPD).Method: 57 pregnant women were recruited in the last trimester of pregnancy, 20 diagnosed with hypertensive disease of pregnancy and 37 normotensive pregnant women. Urinary iodine concentration (UIC), TSH, free T4 (fT4), total antioxidant status (FRP), Superoxide dismutase (SOD), Catalase (CAT), and oxidative stress (TBARS) were evaluated by colorimetric methods.Results: UIC median for all pregnant women was of 151.9 µg / L. The UIC median for pregnant women with HPD was between 50-149 µg/L compared to 150-249 µg/L in normotensive women. No significant changes were found in levels of TSH and fT4 in normotensive pregnant compared with HPD women. Pregnant women with HPD had significant high levels of TBARS, and significant low levels of FRP, SOD, CAT and UIC compared to normotensive pregnant. In addition, pregnant women with optimal levels of UIC had a higher SOD activity (R = 0.354, P = 0.011), while iodine deficiency was associated with HPD (R = -0,281, p = 0.039). Similarly, pregnant with HPD had a significant negative association with SOD activity (R = -0,702, p = 0.005), CAT (R = -0,409, p = 0.002), and FRP (R = -0,624, p = 0.003), and a positive association with TBARS (R = 0.744, p = 0.001).Conclusion: iodine contributes to REDOX balance during pregnancy; its deficiency is associated with HPD. This study shows the importance of iodine during pregnancy.

Iodine is an essential element trace for the synthesis of maternal thyroid hormones needed to support normal fetal development; it also acts as an antioxidant directly or induce antioxidant enzymes indirectly. Iodine deficiency and oxidative stress are associated with pregnancy complications. This study aimed to assess the urinary iodine concentration and its relationship with the antioxidant and oxidative stress status during gestation. Pregnant women were consecutively recruited from an obstetric clinic during all gestation trimesters, and urinary iodine concentration, antioxidant, and oxidative stress were determined. Results showed that 70 % of pregnant women have optimal iodine levels (150-200 μg/L), while approximately 30 % showed mild iodine deficiency (50-99 μg/L). Oxidative stress was significantly higher, and the antioxidant status was also compromised as evidenced by decreased total antioxidant status and superoxide dismutase (SOD) activity in pregnant women with mild iodine deficiency than pregnant women with optimal iodine levels. Significant positive correlations were noted between optimal iodine levels and total antioxidant status. Oxidative stress was significantly correlated with mild iodine deficiency. However, no significant correlation was found between iodine levels and SOD and catalase activities. In conclusion, for the first time, these data suggest a correlation between iodine levels and the antioxidant status during pregnancy.

Iodine deficiency is associated with oxidative stress increase and preeclampsia during gestation, suggesting that iodine concentration plays an important role in the normal placenta physiology. The question raised is to analyze the effect of iodine deficiency on oxidative stress, viability, differentiation, and migration process and changes in the expression of differentiation and migration markers. Iodine deprivation was done using potassium perchlorate (KCLO4) to block sodium iodide symporter (NIS) transporter and 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid DIDS to inhibit pendrine (PEN) transport for 3-48 h. Then trophoblast cells were treated with low iodine doses of 5-500 μM and high iodine doses of 100-5000 μM. Oxidative stress, viability, and human chorionic gonadotropin (hGC) were measured by colorimetric methods. Migration throphoblast cells were evaluated by both wound healing and Boyden chamber assays. Changes in mRNA expression were analyzed by real-time RT-PCR. Iodine deprivation induces a significant increase of reactive oxygen species (ROS), viability, and migration process vs control cells. We found a significant overregulation in the mRNA's peroxisome proliferator-activated receptor (PPAR-gamma), Snail, and matrix metalloproteinase-9 (MMP-9) mRNA's in cells deprived of iodine, as well as a down glial cell missing-1 (GCM-1) regulation, hGC, pregnancy-associated plasma protein-A (PAPP-A), and E-cadherin mRNA expression. The expression of hypoxic induction factor alpha (HIFα) mRNA does not change with iodine deprivation. In cells deprived of iodine, supplementing low iodine doses (5-500 μM) does not induce any significant changes in viability. However, ROS and migration process were decreased, although we found an increased human chorionic gonadotropin (hCG) secretion as a differentiation marker. In addition, we found that PPAR-gamma, Snail, and MPP-9 mRNAs expression are downregulated with low iodine doses, in contrast with GCM-1, PAPP-A, hGC, and E-cadherin that increase their expression vs cells deprived of iodine. High iodine doses (1000-5000 μM) have shown cytotoxic effects. Based on our results, iodine is important for keeping the proliferation/differentiation balance in the placenta.