Effect of MPTP and salsolinol on tissue transglutaminase expression in cultured human dopaminergic SH‐SY5Y cells

Abstract

Tissue transglutaminase (tTG) expression is increased in the brains and cerebrospinal fluid of patients with Parkinson's disease, suggesting a role for the protein in the neurodegenerative process. tTG is a multifunctional protein that catalyzes post‐translational modification of proteins, resulting in the formation of insoluble protein cross linkage or the incorporation of polyamines into protein substrates, and also functions as a G protein hydrolyzing GTP and ATP. The goal of the present study is to determine whether tTG expression is altered in dopaminergic cells following exposure to toxins linked to Parkinson's disease. Immuocytochemistry using a tTG‐specific antibody was used to compare tTG expression in cultured human dopaminergic SH‐SY5Y cells before and after exposure to the environmental toxin 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPTP) and the endogenous dopamine‐derived neurotoxin salsolinol. Both toxins significantly increased tTG expression in SH‐SY5Y cells, suggesting a direct effect of toxins on tTG expression. Further investigations are necessary to determine whether the upregulation of tTG is correlated with increased tTG activity.This work was supported by Touro University Nevada Research Grant Award.