Thyroid hormone T3 induces Fyn modification and modulates palmitoyltransferase gene expression through αvβ3 integrin receptor in PC12 cells during hypoxia.

Autor:	Kvergelidze E; Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, 0162, Georgia., Barbakadze T; Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, 0162, Georgia.; Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, 0160, Georgia., Bátor J; Department of Medical Biology and Central Electron Microscopic Laboratory, Medical School, University of Pécs, Pécs, 7624, Hungary.; Janos Szentagothai Research Centre, University of Pécs, Pécs, 7624, Hungary., Kalandadze I; Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, 0160, Georgia., Mikeladze D; Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, 0162, Georgia.; Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, 0160, Georgia.
Jazyk:	angličtina
Zdroj:	Translational neuroscience [Transl Neurosci] 2024 Aug 07; Vol. 15 (1), pp. 20220347. Date of Electronic Publication: 2024 Aug 07 (Print Publication: 2024).
DOI:	10.1515/tnsci-2022-0347
Abstrakt:	Thyroid hormones (THs) are essential in neuronal and glial cell development and differentiation, synaptogenesis, and myelin sheath formation. In addition to nuclear receptors, TH acts through αvβ3-integrin on the plasma membrane, influencing transcriptional regulation of signaling proteins that, in turn, affect adhesion and survival of nerve cells in various neurologic disorders. TH exhibits protective properties during brain hypoxia; however, precise intracellular mechanisms responsible for the preventive effects of TH remain unclear. In this study, we investigated the impact of TH on integrin αvβ3-dependent downstream systems in normoxic and hypoxic conditions of pheochromocytoma PC12 cells. Our findings reveal that triiodothyronine (T3), acting through αvβ3-integrin, induces activation of the JAK2/STAT5 pathway and suppression of the SHP2 in hypoxic PC12 cells. This activation correlates with the downregulation of the expression palmitoyltransferase-ZDHHC2 and ZDHHC9 genes, leading to a subsequent decrease in palmitoylation and phosphorylation of Fyn tyrosine kinase. We propose that these changes may occur due to STAT5-dependent epigenetic silencing of the palmitoyltransferase gene, which in turn reduces palmitoylation/phosphorylation of Fyn with a subsequent increase in the survival of cells. In summary, our study provides the first evidence demonstrating the involvement of integrin-dependent JAK/STAT pathway, SHP2 suppression, and altered post-translational modification of Fyn in protective effects of T3 during hypoxia. Competing Interests: Conflict of interest: Authors state no conflict of interest. (© 2024 the author(s), published by De Gruyter.)
Databáze:	MEDLINE
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