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

Abstract

Objective: Thyroid hormones are involved in the pathogenesis of various neurological disorders. Ischemia/hypoxiathat induces rigidity of the actin filaments, which initiates neurodegeneration and reduces synaptic plasticity. Wehypothesized that thyroid hormones via alpha-v-beta-3 (αvβ3) integrin could regulate the actin filament rearrangementduring hypoxia and increase neuronal cell viability.Materials and Methods: In this experimental study, we analysed the dynamics of actin cytoskeleton according tothe 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 electrophoresisand western blotting methods. We assessed NADPH oxidase activity under the hypoxic condition by the luminometricmethod 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-dependentdownstream 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

• actin filament
• hypoxia
• integrin
• pc-12
• thyroid hormone