Submitted Successfully!
To reward your contribution, here is a gift for you: A free trial for our video production service.
Thank you for your contribution! You can also upload a video entry or images related to this topic.
Version Summary Created by Modification Content Size Created at Operation
1
Salvatore Ulisse
 + 1657 word(s) 1657 2021-12-20 09:19:38 |
2 The format is correct
Lindsay Dong
 Meta information modification 1657 2022-01-13 02:54:26 |

Video Upload Options

We provide professional Video Production Services to translate complex research into visually appealing presentations. Would you like to try it?
No, upload directly Yes

Confirm

Are you sure to Delete?
Yes No
Cite
If you have any further questions, please contact Encyclopedia Editorial Office.
Ulisse, S. Iodine in Thyroid Hormone Biosynthesis and Beyond. Encyclopedia. Available online: https://encyclopedia.pub/entry/18135 (accessed on 16 November 2024).
Ulisse S. Iodine in Thyroid Hormone Biosynthesis and Beyond. Encyclopedia. Available at: https://encyclopedia.pub/entry/18135. Accessed November 16, 2024.
Ulisse, Salvatore. "Iodine in Thyroid Hormone Biosynthesis and Beyond" Encyclopedia, https://encyclopedia.pub/entry/18135 (accessed November 16, 2024).
Ulisse, S. (2022, January 12). Iodine in Thyroid Hormone Biosynthesis and Beyond. In Encyclopedia. https://encyclopedia.pub/entry/18135
Ulisse, Salvatore. "Iodine in Thyroid Hormone Biosynthesis and Beyond." Encyclopedia. Web. 12 January, 2022.
Iodine in Thyroid Hormone Biosynthesis and Beyond
Edit
This entry is adapted from the peer-reviewed paper 10.3390/nu13124469

The main biological function of iodine concerns its role in the biosynthesis of thyroid hormones (THs) by the thyroid gland. In addition, iodine is thought to represent one of the oldest antioxidants in living organisms. Moreover, iodine oxidation to hypoiodite (IO−) has been shown to possess strong bactericidal as well as antiviral and antifungal activity. Finally, and importantly, iodine has been demonstrated to exert antineoplastic effects in human cancer cell lines.

iodine thyroid hormone biosynthesis

1. Introduction

The term iodine comes from the French word “iode” originally proposed by J.P. Gay-Lussac, derived from the Greek “ἰοειδής” due to its characteristic violet color in its gaseous state [1]. Historically, the only biological function attributed to iodine concerned its incorporation into thyroid hormones (THs), synthesized by the thyroid gland [1]. THs, namely T4 (3,5,3′,5′-tetraiodo-L-thyronine) and T3 (3,5,3′-triiodo-L-thyronine), are characterized by the presence of four and three iodine atoms within the molecule, respectively, and play a prominent role in human body development and homeostasis [2][3]. In addition, over the last two decades, additional physiological roles of iodine have emerged [4][5][6][7]. Specifically, iodine is thought to represent one of the oldest terrestrial antioxidants used by living organisms due to its significant activity as a scavenger of reactive oxygen species (ROS) [5]. Moreover, iodine oxidation to hypoiodite (IO−) possesses strong bactericidal as well as antiviral and antifungal activity [6][7][8][9]. Finally, iodine has been demonstrated to exert antineoplastic effects in breast cancer, and in human melanoma- and lung cancer-derived cell lines [4][10][11][12][13][14].

2. Iodine Metabolism

Iodine is mainly ingested as iodide (I−); iodate (IO3−), which is generally used in salt iodization; or organically bound iodine. More than 90% of ingested iodide is absorbed in the duodenum [1][4][15]. Iodate is reduced in the gut to iodide before absorption, whereas the organically bound iodine is digested, and the released iodide is absorbed [1]. The uptake is mediated by the sodium/iodide symporter (NIS), present on the apical plasma membrane of enterocytes of the duodenum, jejunum, and ileum [16][17][18]. Moreover, other carriers expressed on the brush border of enterocytes are thought to contribute to iodide absorption in the gut, including the sodium multivitamin transporter (SMVT) and the cystic fibrosis transmembrane conductance regulator (CFTR) [4][19][20]. Once absorbed, iodide is transferred to the bloodstream through molecular mechanisms that are still to be fully clarified [4]. In addition to intestinal absorption, deiodination of T4 and T3 by deiodinases in peripheral tissues contributes to the level of iodide present in the bloodstream [21]. Circulating iodide is either taken up by the thyroid gland through the action of NIS, present in the basolateral plasma membrane of thyrocytes, or eliminated in the urine. Inside the kidney, NIS expression was first localized by means of immunohistochemistry in the basolateral membrane of distal tubular cells, suggesting their role in iodide excretion [22]. However, different results were obtained in subsequent studies in which NIS expression was observed on the apical membrane of cells belonging to proximal and cortical collecting tubes, indicating a resorption action of iodide from the urine [4][23]. Thus, the urinary excretion of iodine could be the result of these two opposite processes.

3. Iodine Metabolism in the Thyroid

As mentioned, the main physiological function of iodine concerns TH biosynthesis by the thyroid gland [1]. Bloodstream iodide is actively transported across the plasma membrane into the cytoplasm of thyrocytes by NIS, exploiting the concentration gradient of Na+ generated by the Na+/K+-ATPase transporter as a driving force [23][24]. Iodide is then transferred to the lumen of thyroid follicles by several transporters, including PENDRIN, ANO1, and CFTR [25][26][27][28]. Here, at the outer surface of the apical membranes of thyrocytes, the biosynthesis of THs is initiated by thyroid peroxidase (TPO), which uses H2O2 produced by DUOX2 to oxidize iodide to iodine radicals and incorporates it on specific tyrosine residues within thyrocyte-secreted thyroglobulin (Tg) molecules [29]. After that, TPO couples two residues of diiodotyrosine (DIT) to form thyroxine (T4), and one monoiodotyrosine (MIT) to one DIT to form thyroxine (T3). Mature Tg, containing THs, is stored in the colloid of the follicular lumen. The secretion of THs relies on Tg reabsorption from the lumen by micropinocytosis, and its proteolysis by lysosomal enzymes that release THs from the Tg protein [29]. Uncoupled MIT or DIT residues are deiodinated by the iodotyrosine dehalogenase (DEHAL1), a transmembrane protein localized mainly at the apical pole of thyrocytes and involved in the intrathyroidal recycling of iodide [30]. THs are transported outside the basolateral membrane of thyrocytes, mainly by monocarboxylate transporter 8 (MCT8), from which they reach the bloodstream. The pituitary thyroid stimulating hormone (TSH), through its receptor (TSHR) present on the basolateral surfaces of thyrocytes, is the mainly regulator of TH biosynthesis, controlling the expression of the thyroid-specific genes involved in TH biosynthesis [4][29].

4. Consequences of Iodine Deficiency

Iodine deficiency has several detrimental effects on human growth and development [1][31][32]. About four decades ago, Basil S. Hetzel first coined the term “iodine deficiency disorders” (IDD), recognizing how the negative consequences of a poor dietary iodine intake extended far beyond simple goiter [33][34][35]. As summarized in Table 1, the health risks associated with iodine deficiency may persist throughout the lifetime.
Table 1. Iodine deficiency disorders at different ages. Adapted from [1][36][37].
Age Iodine Deficiency Disorders
Fetus Abortions, stillbirths, congenital anomalies
Increased perinatal mortality
Neonate Neonatal hypothyroidism, endemic cretinism
Increased susceptibility of the thyroid gland to nuclear radiation
Child and
adolescent		 Goiter, hypothyroidism or hyperthyroidism
Impaired mental function, delayed growth and puberty
Increased susceptibility of the thyroid gland to nuclear radiation
Adult Goiter with its complications, hypothyroidism
Infertility, Impaired mental function
Spontaneous hyperthyroidism in the elderly
Iodine-induced hyperthyroidism
Increased susceptibility of the thyroid gland to nuclear radiation

As can be seen in Table 1, hypothyroidism consequent to iodine deficiency in women causes important reproductive alterations including anovulation and reduced fertility and, when pregnancy occurs, gestational hypertension, stillbirths, and congenital anomalies, and increased perinatal mortality may be observed [37]. This may have cultural and socioeconomic consequences, compromising the life quality of parents that face the responsibility of taking care of a child with serious health problems [37][38]. From a physiological point of view, infertility occurring in iodine-deficient hypothyroid women could be seen as a protective mechanism implemented by the body to avoid hazards related to pregnancies carried out in iodine deficiency conditions. Recently, data indicating a direct association between iodine status and fertility have been reported by Mills and colleagues [39]. They observed that the time to pregnancy was significantly delayed in women with preconception UIC values <50 μg/L, with a fecundability odds ratio reduced by 46% over each menstrual cycle [39]. The detrimental effects of iodine deficiency on the development and maturation of the fetal brain are of particular relevance, representing a major preventable cause of mental defects [1][31][32][40][41][42][43][44][45][46][47].

5. Iodine Functions against Pathogens

In the salivary glands, stomach, and intestine, iodide is thought to take part in innate immune defense [4]. In these tissues, iodide may be recycled from the bloodstream and eventually re-absorbed again by the epithelial cells of the duodenum, jejunum, and ileum [4]. In the salivary glands and in the mucin-secreting and parietal cells of the stomach, iodide uptake from the bloodstream is mediated by the NIS present on the basolateral membrane of the cells, and secreted in saliva and gastric juices by low-affinity iodide transporters on the apical plasma membranes, such as CFTR, ANO1, and PENDRIN [4][8][48][49][50][51][52][53]. The presence of DUOX2 in the apical membrane of epithelial salivary cells, of the gastric mucosa, and of the apical surface of enterocytes, along with that of tissue-specific peroxidase (salivary peroxidase, gastric peroxidase, and lactoperoxidase (LPO) in the intestinal mucus) in these sites allow for iodide oxidation to hypoiodite (IO−), which is endowed with fungicidal and bactericidal activity [4][6][7][8][48][49][50][51][52][53]. In addition, through a similar mechanism to that described above, iodide oxidation has been shown to possess a strong antiviral action against lung adenoviruses [4][9].

6. Iodine and Cancer

Several experimental findings have indicated that iodide may elicit antiproliferative and apoptotic effects in malignant cells [4]. Vitale and colleagues reported the ability of an excess of iodide (KI) to induce apoptosis of immortalized thyroid cells and primary cultures of human thyrocytes, but not of extrathyroidal cells [54]. The apoptotic effect of thyroid cells was p53-independent and required the presence of a functional thyroid peroxidase as its inhibition by propylthiouracil completely prevented iodide-induced apoptosis [9]. Later on, Zhang and colleagues confirmed the ability of iodide to induce apoptosis of lung cancer cells transfected with NIS and TPO, but not in those transfected only with NIS [55]. Altogether, this evidence indicates that iodide needs to be oxidized to induce apoptosis. García-Solís and colleagues analyzed the effect of molecular iodine (I2) and iodide (KI) on the induction and promotion of mammary cancer induced by N-Methyl-N-nitrosourea in rats [56]. They found that I2, but not iodide, had a potent antineoplastic effect on the progression of mammary cancer. This antineoplastic effect was thought to be mediated by I2-induced expression of the peroxisome proliferator-activated receptor γ (PPARγ), which is capable of triggering the apoptosis of malignant cells [56][57][58]. The observation that iodide had no effects in this experimental system was explained by the lack or low expression of NIS and/or LPO. In a different human mammary cancer model, using dimethylbenz[a]anthracene (DMBA)-induced mammary tumors, the tumor cells were shown to express both NIS and LPO [59]. In this experimental model the co-administration of iodine and/or iodide along with medroxyprogesterone acetate (MPA) inhibited mammary cancer growth at a significantly higher level with respect to MPA alone [60][61]. In particular, the higher growth inhibitory effects were observed in tumor tissues with a higher iodine content, indicating that direct iodine uptake by breast tumors led to the suppression of tumor growth [60]. More recently, iodine supplementation was found to enhance the antineoplastic effect of doxorubicin in canine patients affected by mammary cancers [13][14]. In particular, co-treatment with doxorubicin and I2 has been shown to improve therapeutic outcomes, diminish the invasive capacity, attenuate adverse events, and increase disease-free survival. The antiproliferative and apoptotic effects of iodine were further confirmed in thymic epithelial tumour cells and different human colon cancer cell lines [11][12]. Altogether, this experimental evidence clearly suggests that iodine may positively contribute to the fight against cancer.

References

  1. Zimmermann, M.B. Iodine Deficiency. Endocr. Rev. 2009, 30, 376–408.
  2. Mendoza, A.; Hollenberg, A.N. New insights into thyroid hormone action. Pharmacol. Ther. 2017, 173, 135–145.
  3. Brent, G.A. Mechanisms of thyroid hormone action. J. Clin. Investig. 2012, 122, 3035–3043.
  4. De la Vieja, A.; Santisteban, P. Role of iodine metabolism in physiology and cancer. Endocr. Relat. Cancer 2018, 25, R225–R245.
  5. Venturi, S.; Venturi, M. Iodide, thyroid and stomach carcinogenesis: Evolutionary story of a primitive antioxidant? Eur. J. Endocrinol. 1999, 140, 371–372.
  6. Bosch, E.H.; van Doorne, H.; de Vries, S. The lactoperoxidase system: The influence of iodide and the chemical and antimicrobial stability over the period of about 18 months. J. Appl. Microbiol. 2000, 89, 215–224.
  7. Huang, Y.Y.; Choi, H.; Kushida, Y.; Bhayana, B.; Wang, Y.; Hamblin, M.R. Broad-Spectrum Antimicrobial Effects of Photocatalysis Using Titanium Dioxide Nanoparticles Are Strongly Potentiated by Addition of Potassium Iodide. Antimicrob. Agents Chemother. 2016, 60, 5445–5453.
  8. Ihalin, R.; Loimaranta, V.; Tenovuo, J. Origin, structure, and biological activities of peroxidases in human saliva. Arch. Biochem. Biophys. 2006, 445, 261–268.
  9. Fischer, A.J.; Lennemann, N.J.; Krishnamurthy, S.; Pócza, P.; Durairaj, L.; Launspach, J.L.; Rhein, B.A.; Wohlford-Lenane, C.; Lorentzen, D.; Bánfi, B.; et al. Enhancement of respiratory mucosal antiviral defenses by the oxidation of iodide. Am. J. Respir. Cell Mol. Biol. 2011, 45, 874–881.
  10. Aceves, C.; Anguiano, B.; Delgado, G. The extrathyronine actions of iodine as antioxidant, apoptotic, and differentiation factor in various tissues. Thyroid 2013, 23, 938–946.
  11. Rösner, H.; Möller, W.; Groebner, S.; Torremante, P. Antiproliferative/cytotoxic effects of molecular iodine, povidone-iodine and Lugol’s solution in different human carcinoma cell lines. Oncol. Lett. 2016, 12, 2159–2162.
  12. Lee, H.S.; Jang, H.J.; Lo, E.M.; Truong, C.Y.; Groth, S.S.; Friedberg, J.S.; Sugarbaker, D.J.; Burt, B.M. Povidone-iodine results in rapid killing of thymic epithelial tumour cells through cellular fixation. Interact. Cardiovasc. Thorac. Surg. 2019, 28, 353–359.
  13. Zambrano-Estrada, X.; Landaverde-Quiroz, B.; Dueñas-Bocanegra, A.A.; De Paz-Campos, M.A.; Hernández-Alberto, G.; Solorio-Perusquia, B.; Trejo-Mandujano, M.; Pérez-Guerrero, L.; Delgado-González, E.; Anguiano, B.; et al. Molecular iodine/doxorubicin neoadjuvant treatment impair invasive capacity and attenuate side effect in canine mammary cancer. BMC Vet. Res. 2018, 14, 87.
  14. Cuenca-Micó, O.; Aceves, C. Micronutrients and Breast Cancer Progression: A Systematic Review. Nutrients 2020, 12, 3613.
  15. Alexander, W.D.; Harden, R.M.; Harrison, M.T.; Shimmins, J. Some aspects of the absorption and concentration of iodide by the alimentary tract in man. Proc. Nutr. Soc. 1967, 26, 62–66.
  16. Ravera, S.; Reyna-Neyra, A.; Ferrandino, G.; Amzel, L.M.; Carrasco, N. The Sodium/Iodide Symporter (NIS): Molecular Physiology and Preclinical and Clinical Applications. Annu. Rev. Physiol. 2017, 79, 261–289.
  17. Nicola, J.P.; Basquin, C.; Portulano, C.; Reyna-Neyra, A.; Paroder, M.; Carrasco, N. The Na+/I− symporter mediates active iodide uptake in the intestine. Am. J. Physiol. Cell Physiol. 2009, 296, C654–C662.
  18. Mitsuma, T.; Rhue, N.; Hirooka, Y.; Kayama, M.; Yokoi, Y.; Mori, Y.; Ping, J.; Adachi, K.; Wago, T.; Ohtake, M.; et al. Organ distribution of iodide transporter (symporter) in the rat: Immunohistochemical study. Endocr. Regul. 1997, 31, 15–18.
  19. Prasad, P.D.; Wang, H.; Huang, W.; Fei, Y.J.; Leibach, F.H.; Devoe, L.D.; Ganapathy, V. Molecular and functional characterization of the intestinal Na+-dependent multivitamin transporter. Arch. Biochem. Biophys. 1999, 366, 95–106.
  20. Strong, T.V.; Boehm, K.; Collins, F.S. Localization of cystic fibrosis transmembrane conductance regulator mRNA in the human gastrointestinal tract by in situ hybridization. J. Clin. Investig. 1994, 93, 347–354.
  21. Bianco, A.C.; da Conceição, R.R. The deiodinase trio and thyroid hormone signaling. Methods Mol. Biol. 2018, 1801, 67–83.
  22. Spitzweg, C.; Dutton, C.M.; Castro, M.R.; Bergert, E.R.; Goellner, J.R.; Heufelder, A.E.; Morris, J.C. Expression of the sodium iodide symporter in human kidney. Kidney Int. 2001, 59, 1013–1023.
  23. Wapnir, I.L.; van de Rijn, M.; Nowels, K.; Amenta, P.S.; Walton, K.; Montgomery, K.; Greco, R.S.; Dohán, O.; Carrasco, N. Immunohistochemical profile of the sodium/iodide symporter in thyroid, breast, and other carcinomas using high density tissue microarrays and conventional sections. J. Clin. Endocrinol. Metab. 2003, 88, 1880–1888.
  24. Spitzweg, C.; Joba, W.; Schriever, K.; Goellner, J.R.; Morris, J.C.; Heufelder, A.E. Analysis of human sodium iodide symporter immunoreactivity in human exocrine glands. J. Clin. Endocrinol. Metab. 1999, 84, 4178–4184.
  25. Shcheynikov, N.; Yang, D.; Wang, Y.; Zeng, W.; Karniski, L.P.; So, I.; Wall, S.M.; Muallem, S. The Slc26a4 transporter functions as an electroneutral Cl-/I-/HCO3- exchanger: Role of Slc26a4 and Slc26a6 in I- and HCO3- secretion and in regulation of CFTR in the parotid duct. J. Physiol. 2008, 586, 3813–3824.
  26. Kopp, P.; Pesce, L.; Solis, S.J.C. Pendred syndrome and iodide transport in the thyroid. Trends Endocrinol. Metab. 2008, 19, 260–268.
  27. Devuyst, O.; Golstein, P.E.; Sanches, M.V.; Piontek, K.; Wilson, P.D.; Guggino, W.B.; Dumont, J.E.; Beauwens, R. Expression of CFTR in human and bovine thyroid epithelium. Am. J. Physiol. 1997, 272, C1299–C1308.
  28. Twyffels, L.; Strickaert, A.; Virreira, M.; Massart, C.; Van Sande, J.; Wauquier, C.; Beauwens, R.; Dumont, J.E.; Galietta, L.J.; Boom, A.; et al. Anoctamin-1/TMEM16A is the major apical iodide channel of the thyrocyte. Am. J. Physiol. Cell Physiol. 2014, 307, C1102–C1112.
  29. Carvalho, D.P.; Dupuy, C. Thyroid hormone biosynthesis and release. Mol. Cell. Endocrinol. 2017, 458, 6–15.
  30. Gnidehou, S.; Caillou, B.; Talbot, M.; Ohayon, R.; Kaniewski, J.; Noël-Hudson, M.S.; Morand, S.; Agnangji, D.; Sezan, A.; Courtin, F.; et al. Iodotyrosine dehalogenase 1 (DEHAL1) is a transmembrane protein involved in the recycling of iodide close to the thyroglobulin iodination site. FASEB J. 2004, 18, 1574–1576.
  31. WHO; UNICEF; ICCIDD. Assessment of Iodine Deficiency Disorders and Monitoring Heir Elimination; WHO Press, World Health Organization: Geneva, Swizterland, 2007; Available online: https://www.who.int/nutrition/publications/micronutrients/iodine_deficiency/WHO_NHD_01.1/en/ (accessed on 23 December 2020).
  32. Iodine Global Network. Guidance on the Monitoring of Salt Iodization Programmes and Determination of Population Iodine Status. Available online: https://www.ign.org/p142003099.html?from=0142002801 (accessed on 13 December 2021).
  33. Hetzel, B.S. Iodine deficiency disorders (IDD) and their eradication. Lancet 1983, 2, 1126–1129.
  34. Hetzel, B.S. Iodine-deficiency disorders. Lancet 1988, 1, 1386–1387.
  35. Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S. Iodine-deficiency disorders. Lancet 2008, 372, 1251–1262.
  36. Coccaro, C.; Tuccilli, C.; Prinzi, N.; D’Armiento, E.; Pepe, M.; Del Maestro, F.; Cacciola, G.; Forlini, B.; Verdolotti, S.; Bononi, M.; et al. Consumption of iodized salt may not represent a reliable indicator of iodine adequacy: Evidence from a cross-sectional study on schoolchildren living in an urban area of central Italy. Nutrition 2016, 32, 662–666.
  37. Dunn, J.T.; Delange, F. Damaged reproduction: The most important consequence of iodine deficiency. J. Clin. Endocrinol. Metab. 2001, 86, 2360–2363.
  38. Ferri, N.; Ulisse, S.; Aghini-Lombardi, F.; Graziano, F.M.; Di Mattia, T.; Russo, F.P.; Arizzi, M.; Baldini, E.; Trimboli, P.; Attanasio, D.; et al. Iodine supplementation restores fertility of sheep exposed to iodine deficiency. J. Endocrinol. Investig. 2003, 26, 1081–1087.
  39. Mills, J.L.; Buck Louis, G.M.; Kannan, K.; Weck, J.; Wan, Y.; Maisog, J.; Giannakou, A.; Wu, Q.; Sundaram, R. Delayed conception in women with low-urinary iodine concentrations: A population-based prospective cohort study. Hum. Reprod. 2018, 33, 426–433.
  40. Delange, F. Iodine deficiency as a cause of brain damage. Postgrad. Med. J. 2001, 77, 217–720.
  41. Salazar, P.; Cisternas, P.; Martinez, M.; Inestrosa, N.C. Hypothyroidism and cognitive disorders during development and adulthood: Implications in the central nervous system. Mol. Neurobiol. 2019, 56, 2952–2963.
  42. Walsh, V.; Brown, J.V.E.; McGuire, W. Iodine supplementation for the prevention of mortality and adverse neurodevelopmental outcomes in preterm infants. Cochrane Database Syst. Rev. 2019, 2, CD005253.
  43. Farebrother, J.; Naude, C.E.; Nicol, L.; Sang, Z.; Yang, Z.; Jooste, P.L.; Andersson, M.; Zimmermann, M.B. Effects of Iodized Salt and Iodine Supplements on Prenatal and Postnatal Growth: A Systematic Review. Adv. Nutr. 2018, 9, 219–237.
  44. McCarrison, R. Observations on Endemic Cretinism in the Chitral and Gilgit Valleys. Ind. Med. Gaz. 1908, 43, 441–449.
  45. Pharoah, P.O.; Buttfield, I.H.; Hetzel, B.S. Neurological damage to the fetus resulting from severe iodine deficiency during pregnancy. Lancet 1971, 1, 308–310.
  46. Haddow, J.E.; Palomaki, G.E.; Allan, W.C.; Williams, J.R.; Knight, G.J.; Gagnon, J.; O’Heir, C.E.; Mitchell, M.L.; Hermos, R.J.; Waisbren, S.E.; et al. Maternal thyroid deficiency during pregnancy and subsequent neuropsychological development of the child. N. Engl. J. Med. 1999, 341, 549–555.
  47. Jansen, T.A.; Korevaar, T.I.M.; Mulder, T.A.; White, T.; Muetzel, R.L.; Peeters, R.P.; Tiemeier, H. Maternal thyroid function during pregnancy and child brain morphology: A time window-specific analysis of a prospective cohort. Lancet Diabetes Endocrinol. 2019, 7, 629–637.
  48. Perez-Cornejo, P.; Gokhale, A.; Duran, C.; Cui, Y.; Xiao, Q.; Hartzell, H.C.; Faundez, V. Anoctamin 1 (Tmem16A) Ca2+-activated chloride channel stoichiometrically interacts with an ezrin-radixin-moesin network. Proc. Natl. Acad. Sci. USA 2012, 109, 10376–10381.
  49. Altorjay, A.; Dohán, O.; Szilágyi, A.; Paroder, M.; Wapnir, I.L.; Carrasco, N. Expression of the Na+/I− symporter (NIS) is markedly decreased or absent in gastric cancer and intestinal metaplastic mucosa of Barrett esophagus. BMC Cancer 2007, 7, 5.
  50. Mazzone, A.; Bernard, C.E.; Strege, P.R.; Beyder, A.; Galietta, L.J.; Pasricha, P.J.; Rae, J.L.; Parkman, H.P.; Linden, D.R.; Szurszewski, J.H.; et al. Altered expression of Ano1 variants in human diabetic gastroparesis. J. Biol. Chem. 2011, 286, 13393–13403.
  51. Riesco-Eizaguirre, G.; Santisteban, P. New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy. Endocr. Relat. Cancer 2007, 14, 957–977.
  52. Scott, D.A.; Wang, R.; Kreman, T.M.; Sheffield, V.C.; Karniski, L.P. The Pendred syndrome gene encodes a chloride-iodide transport protein. Nat. Genet. 1999, 21, 440–443.
  53. van der Vliet, A.; Tuinstra, T.J.; Bast, A. Modulation of oxidative stress in the gastrointestinal tract and effect on rat intestinal motility. Biochem. Pharmacol. 1989, 38, 2807–2818.
  54. Vitale, M.; Di Matola, T.; D’Ascoli, F.; Salzano, S.; Bogazzi, F.; Fenzi, G.; Martino, E.; Rossi, G. Iodide excess induces apoptosis in thyroid cells through a p53-independent mechanism involving oxidative stress. Endocrinology 2000, 141, 598–605.
  55. Zhang, L.; Sharma, S.; Zhu, L.X.; Kogai, T.; Hershman, J.M.; Brent, G.A.; Dubinett, S.M.; Huang, M. Nonradioactive iodide effectively induces apoptosis in genetically modified lung cancer cells. Cancer Res. 2003, 63, 5065–5072.
  56. García-Solís, P.; Alfaro, Y.; Anguiano, B.; Delgado, G.; Guzman, R.C.; Nandi, S.; Díaz-Muñoz, M.; Vázquez-Martínez, O.; Aceves, C. Inhibition of N-methyl-N-nitrosourea-induced mammary carcinogenesis by molecular iodine (I2) but not by iodide (I-) treatment Evidence that I2 prevents cancer promotion. Mol. Cell. Endocrinol. 2005, 236, 49–57.
  57. Shrivastava, A.; Tiwari, M.; Sinha, R.A.; Kumar, A.; Balapure, A.K.; Bajpai, V.K.; Sharma, R.; Mitra, K.; Tandon, A.; Godbole, M.M. Molecular iodine induces caspase-independent apoptosis in human breast carcinoma cells involving the mitochondria-mediated pathway. J. Biol. Chem. 2006, 281, 19762–19771.
  58. Aceves, C.; García-Solís, P.; Arroyo-Helguera, O.; Vega-Riveroll, L.; Delgado, G.; Anguiano, B. Antineoplastic effect of iodine in mammary cancer: Participation of 6-iodolactone (6-IL) and peroxisome proliferator-activated receptors (PPAR). Mol. Cancer 2009, 8, 33.
  59. Anderson, W.A.; Perotti, M.E.; McManaway, M.; Lindsey, S.; Eckberg, W.R. Similarities and differences in the ultrastructure of two hormone-dependent and one independent human breast carcinoma grown in athymic nude mice: Comparison with the rat DMBA-induced tumor and normal secretory mammocytes. J. Submicrosc. Cytol. 1984, 16, 673–690.
  60. Funahashi, H.; Imai, T.; Tanaka, Y.; Tobinaga, J.; Wada, M.; Morita, T.; Yamada, F.; Tsukamura, K.; Oiwa, M.; Kikumori, T.; et al. Suppressive effect of iodine on DMBA-induced breast tumor growth in the rat. J. Surg. Oncol. 1996, 61, 209–213.
  61. Soriano, O.; Delgado, G.; Anguiano, B.; Petrosyan, P.; Molina-Servín, E.D.; Gonsebatt, M.E.; Aceves, C. Antineoplastic effect of iodine and iodide in dimethylbenzanthracene-induced mammary tumors: Association between lactoperoxidase and estrogen-adduct production. Endocr. Relat. Cancer 2011, 18, 529–539.
More
© Text is available under the terms and conditions of the Creative Commons Attribution (CC BY) license; additional terms may apply. By using this site, you agree to the Terms and Conditions and Privacy Policy.
Upload a video for this entry
Information
Subjects: Nutrition & Dietetics
Contributor MDPI registered users' name will be linked to their SciProfiles pages. To register with us, please refer to https://encyclopedia.pub/register :
Salvatore Ulisse
View Times: 961
Revisions: 2 times (View History)
Update Date: 13 Jan 2022
Table of Contents
    1000/1000
    Hot Most Recent
    ScholarVision Creations
    Feedback