3,5,3’-triiodo-l-thyronine regulates actin cytoskeleton dynamic in the differentiated pc-12 cells during hypoxia through an αvβ3 integrin

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 rearrangement during 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.