3,5,3'-Triiodo-L-Thyronine Regulates Actin Cytoskeleton Dynamic in The Differentiated PC-12 Cells during Hypoxia through An αvβ3 Integrin

Document Type : Original Article

Authors

1 Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Georgia

2 Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia

3 Department of Medical Biology and Central Electron Microscopic Laboratory, Medical School, University of Pécs, Pécs, Hungary

4 Janos Szentagothai Research Centre, University of Pécs, Pécs, Hungary

5 Faculty of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili Ave., 0162, Tbilisi, Georgia

6 Department of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Str., 0160, Tbilisi, Georgia

Abstract

Objective: Thyroid hormones are involved in the pathogenesis of various neurological disorders. Ischemia/hypoxia
that induces rigidity of the actin filaments, which initiates neurodegeneration and reduces synaptic plasticity. We
hypothesized that thyroid hormones via alpha-v-beta-3 (αvβ3) integrin could regulate the actin filament rearrangement
during hypoxia and increase neuronal cell viability.
Materials and Methods: In this experimental study, we analysed the dynamics of actin cytoskeleton according to
the G/F actin ratio, cofilin-1/p-cofilin-1 ratio, and p-Fyn/Fyn ratio in differentiated PC-12 cells with/without T3 hormone
(3,5,3'-triiodo-L-thyronine) treatment and blocking αvβ3-integrin-antibody under hypoxic conditions using electrophoresis
and western blotting methods. We assessed NADPH oxidase activity under the hypoxic condition by the luminometric
method and Rac1 activity using the ELISA-based (G-LISA) activation assay kit.
Results: The T3 hormone induces the αvβ3 integrin-dependent dephosphorylation of the Fyn kinase (P=0.0010),
modulates the G/F actin ratio (P=0.0010) and activates the Rac1/NADPH oxidase/cofilin-1 (P=0.0069, P=0.0010,
P=0.0045) pathway. T3 increases PC-12 cell viability (P=0.0050) during hypoxia via αvβ3 integrin-dependent
downstream regulation systems.
Conclusion: The T3 thyroid hormone may modulate the G/F actin ratio via the Rac1 GTPase/NADPH oxidase/
cofilin1signaling pathway and αvβ3-integrin-dependent suppression of Fyn kinase phosphorylation.

Keywords

References

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Cell Journal (Yakhteh)
Volume 25, Issue 4
April 2023
Pages 247-254

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