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Vpliv hormona ščitnice T3 na lokalizacijo in dinamiko transporterja LAT2 v astrocitih
Mlinar, Anja (Author), Jorgačevski, Jernej (Mentor) More about this mentor... This link opens in a new window

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Abstract
Astrociti so celice glije, ki na raznolike načine vplivajo na delovanje sosednjih celic; med drugim koordinirajo delovanje živčnih celic in prispevajo k funkciji in integriteti krvno možganske pregrade. Med endokrinim sistemom, ki sprošča hormone, kot so npr. hormoni ščitnice (HŠ), in med centralnim živčnim sistemom (CŽS) je zelo tesna povezava. V CŽS sta prisotna HŠ L-trijodotironin (T3) in L-tiroksin (T4). Folikularne celice ščitnice izločajo predvsem hormon T4 (v manjši meri tudi hormon T3), ki prek krvnega obtoka doseže CŽS. Njegov prenos prek krvno možganske pregrade v astrocite omogočajo posebni transporterji, med katerimi so tudi transporterji aminokislin tipa L (LAT). Znotraj astrocitov se hormon T4 s pomočjo encima deiodinaza tipa 2 pretvori v aktivno obliko T3, ta pa se izloča v medcelični prostor skozi prej omenjene transporterje, med drugim tudi skozi LAT2. Vpliv neravnovesja HŠ na delovanje živčevja je znan, ni pa znano, kako astrociti prispevajo k nastanku nevropsihiatričnih motenj. V raziskavi smo preučili vpliv povišane koncentracije hormona T3 na prerazporejanje transporterja LAT2 v astrocitih, na mobilnost endocitotskih mešičkov, na koncentracijo kalcijevih ionov v astrocitih in na strukturo citoskeleta. Pokazali smo, da dolgotrajna izpostavitev povišanim koncentracijam hormona T3 zmanjša delež transporterja LAT2 na plazmalemi, kar je verjetno posledica uravnavanja z negativno povratno zanko. V skladu s tem se je hitrost endocitotskih mešičkov, ki nosijo transporterje LAT2, povečala ob dolgotrajni izpostavitvi hormonu T3. Poleg tega smo opazili povišanje znotrajcelične koncentracije kalcijevih ionov. Dolgotrajna izpostavitev povišanim koncentracijam hormona T3 je povzročila tudi rahlo depolimerizacijo α-tubulina.

Language:Slovenian
Keywords:astrociti, hormoni ščitnice, hormon T3, transporter LAT2, hipertiroidizem, mobilnost endocitotskih mešičkov, centralni živčni sistem
Work type:Master's thesis/paper (mb22)
Tipology:2.09 - Master's Thesis
Organization:BF - Biotechnical Faculty
Year:2021
Publisher:[A. Mlinar]
Place:Ljubljana
UDC:606:61:577.175.4:577.171.5(043.2)
COBISS.SI-ID:78245635 This link opens in a new window
Views:95
Downloads:18
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Secondary language

Language:English
Title:The effect of T3 thyroid hormone on localization and dynamics of LAT2 in astrocytes
Abstract:
Astrocytes are glial cells with a diverse set of functions; among others they are involved in integrating neuronal functions, and in the maintenance of the blood brain barrier. There is a close relationship between the endocrine system and the central nervous system (CNS). Thyroid hormones (THs) are an important factor in the development and function of the CNS. Thyroid follicular cells secrete mainly the hormone T4 (and to a lesser extent the hormone T3), which enters the CNS via the bloodstream. Its transfer across the blood-brain barrier into astrocytes is facilitated by specialized transporters, including L-type amino acid transporters (LATs). Within astrocytes, the hormone T4 is converted by the enzyme deiodinase type 2 into the active form of T3, which is secreted into the intercellular space through the before mentioned transporters, including through LAT2. The impact of TH imbalance on synaptic transmission and plasticity is known, however, it is unclear how astrocytes contribute to the development of neuropsychological disorders. Here we investigated the effect of elevated concentrations of T3 hormone on the redistribution of the LAT2 transporters in astrocytes, on the mobility of endocytic vesicles, on calcium ion concentration in astrocytes, and on the structure of the cytoskeleton. Long-term exposure to elevated concentrations of the hormone T3 was shown to reduce the proportion of the LAT2 transporter in the plasmalemma. Accordingly, the velocity of endocytic vesicles carrying LAT2 transporter increased with prolonged exposure to elevated concentrations of the hormone T3. In addition, we observed an increase in the concentration of calcium ions. Finally, prolonged exposure to elevated T3 hormone concentrations also resulted in a slight depolymerization of α-tubulin.

Keywords:astrocyte, thyroid hormones, hormone T3, LAT2 transporter, hyperthyroidism, endocytic vesicle mobility, central nervous system

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