Document Type : Original Article
Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Georgia
Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia
Department of Medical Biology and Central Electron Microscopic Laboratory, Medical School, University of Pécs, Pécs, Hungary
Janos Szentagothai Research Centre, University of Pécs, Pécs, Hungary
Faculty of Natural Sciences and Medicine, Ilia State University, 3/5 K. Cholokashvili Ave., 0162, Tbilisi, Georgia
Department of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, 14 Gotua Str., 0160, Tbilisi, Georgia
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.