Redox Properties of 3-Iodothyronamine (T1AM) and 3-Iodothyroacetic Acid (TA1)

Abstract

3-iodothyronamine (T1AM) and 3-iodothyroacetic acid (TA1) are thyroid-hormone-related compounds endowed with pharmacological activity through mechanisms that remain elusive. Some evidence suggests that they may have redox features. We assessed the chemical activity of T1AM and TA1 at pro-oxidant conditions. Further, in the cell model consisting of brown adipocytes (BAs) differentiated for 6 days in the absence (M cells) or in the presence of 20 nM T1AM (M + T1AM cells), characterized by pro-oxidant metabolism, or TA1 (M + TA1 cells), we investigated the expression/activity levels of pro- and anti-oxidant proteins, including UCP-1, sirtuin-1 (SIRT1), mitochondrial monoamine (MAO-A and MAO-B), semicarbazide-sensitive amine oxidase (SSAO), and reactive oxygen species (ROS)-dependent lipoperoxidation. T1AM and TA1 showed in-vitro antioxidant and superoxide scavenging properties, while only TA1 acted as a hydroxyl radical scavenger. M + T1AM cells showed higher lipoperoxidation levels and reduced SIRT1 expression and activity, similar MAO-A, but higher MAO-B activity in terms of M cells. Instead, the M + TA1 cells exhibited increased levels of SIRT1 protein and activity and significantly lower UCP-1, MAO-A, MAO-B, and SSAO in comparison with the M cells, and did not show signs of lipoperoxidation. Our results suggest that SIRT1 is the mediator of T1AM and TA1 pro-or anti-oxidant effects as a result of ROS intracellular levels, including the hydroxyl radical. Here, we provide evidence indicating that T1AM and TA1 administration impacts on the redox status of a biological system, a feature that indicates the novel mechanism of action of these two thyroid-hormone-related compounds.

Thyroid Homeostasis: An Intricate Network of Production, Transport, Metabolism and Receptors Interaction

“…TH-related compounds are a series of molecules that circulate in mammals, exerting effects somehow related with those of TH by mechanisms largely unknown. Gencarelli et al [ 6 ] investigated the redox properties of two TH-related compounds, the 3-iodothyronamine and 3-iodothyroacetic acid (T1AM and TA1, respectively), at chemical settings and in a model of differentiating rat adipocytes. They found that T1AM and TA1, although with minor differences, work as antioxidants and scavengers when exposed to strong pro-oxidant conditions; instead, in the cell model, T1AM and TA1 mediate pro- or anti-oxidant effects, respectively, probably through the inhibition/activation of sirtuin1 and then exerting post-translational control on protein activities.…”