Exogenous 3-Iodothyronamine (TAM) Can Affect Phosphorylation of Proteins Involved on Signal Transduction Pathways in In Vitro Models of Brain Cell Lines, but These Effects Are Not Strengthened by Its Catabolite, 3-Iodothyroacetic Acid (TA).

TAM, a derivative of thyroid hormones, and its major catabolite, TA, produce effects on memory acquisition in rodents. In the present study, we compared the effects of exogenous TAM and TA on protein belonging to signal transduction pathways, assuming that TA may strengthen TAM's effects in brain tissue. A hybrid line of cancer cells of mouse neuroblastoma and rat glioma (NG 108-15), as well as a human glioblastoma cell line (U-87 MG) were used. We first characterized the in vitro model by analyzing gene expression of proteins involved in the glutamatergic cascade and cellular uptake of TAM and TA. Then, cell viability, glucose consumption, and protein expression were assessed. Both cell lines expressed receptors implicated in glutamatergic pathway, namely Nmdar1, Glur2, and EphB2, but only U-87 MG cells expressed TAAR1. At pharmacological concentrations, TAM was taken up and catabolized to TA and resulted in more cytotoxicity compared to TA. The major effect, highlighted in both cell lines, albeit on different proteins involved in the glutamatergic signaling, was an increase in phosphorylation, exerted by TAM but not reproduced by TA. These findings indicate that, in our in vitro models, TAM can affect proteins involved in the glutamatergic and other signaling pathways, but these effects are not strengthened by TA.