Proteomic Analysis of Zn Depletion/Repletion in the Hormone-Secreting Thyroid Follicular Cell Line FRTL-5

Abstract

Zinc deficiency predisposes to a wide spectrum of chronic diseases. The human Zn proteome was predicted to represent about 10% of the total human proteome, reflecting the broad array of metabolic functions in which this micronutrient is known to participate. In the thyroid, Zn was reported to regulate cellular homeostasis, with a yet elusive mechanism. The Fischer Rat Thyroid Cell Line FRTL-5 cell model, derived from a Fischer rat thyroid and displaying a follicular cell phenotype, was used to investigate a possible causal relationship between intracellular Zn levels and thyroid function. A proteomic approach was applied to compare proteins expressed in Zn deficiency, obtained by treating cells with the Zn-specific chelator N,N,N′,N′-tetrakis (2-pyridylmethyl) ethylene-diamine (TPEN), with Zn repleted cells. Quantitative proteomic analysis of whole cell protein extracts was performed using stable isotope dimethyl labelling coupled to nano-ultra performance liquid chromatography-mass spectrometry (UPLC-MS). TPEN treatment led to almost undetectable intracellular Zn, while decreasing thyroglobulin secretion. Subsequent addition of ZnSO4 fully reversed these phenotypes. Comparative proteomic analysis of Zn depleted/repleted cells identified 108 proteins modulated by either treatment. Biological process enrichment analysis identified functions involved in calcium release and the regulation of translation as the most strongly regulated processes in Zn depleted cells.

Nutraceuticals in Thyroidology: A Review of in Vitro, and in Vivo Animal Studies

“…These experimental studies are expected to improve the clinicians' knowledge about the main supplements being used, in order to clarify the potential risks or side effects and support patients in their use. zinc modulation thyroid function [36][37][38][92][93][94][95][96] inositol involvement in the intracellular TSH signaling, via PIP-3 inositol supplementation decreased circulating T3 and FT3 concentrations thyroid diagnostic oncometabolite the treatment, in combination with seleno-methionine, declined the elevated levels of TSH in patients with AIT and subclinical hypothyroidism immune-modulatory effect of myo-inositol in association with seleno-methionine in patients with euthyroid AIT beneficial effects of myo-inositol, seleno-methionine or their combination on PBMC exposed in vitro to H2O2-induced oxidative stress in both control and women with HT protective effect of myo-inositol on thyroid cells myo-inositol, either alone or in association with T3 improved cardiac lipid content and function of streptozocin-induced diabetic rats Funding: This research received no external funding.…”

“…In this experimental setting which would mimic the in vivo condition, Tg secretion was decreased. Proteomic analyses performed comparing data from zinc depleted/repleted thyroid cells have identified 108 proteins modulated by intracellular zinc status with important physiopathological implications for this endocrine tissue [96].…”

Zinc Depletion Inhibits the Synthesis and Secretion of Thyroglobulin by Inducing Endoplasmic Reticulum Stress in PCCL3 Thyroid Cells

“…Congenital hypothyroidism is caused by defective thyroglobulin (Tg) synthesis and folding, which involves ER chaperones [32][33][34]. Limited information is currently available regarding the regulation of Tg synthesis and secretion from thyrocytes by zinc depletion [35]. Moreover, zinc deficiency and ER stress have been associated with various diseases; however, the pathological mechanisms triggered by zinc deficiency and ER stress are poorly known [16,36].…”