Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway.

Resveratrol treatment reduces the vulnerability of SH-SY5Y cells and cortical neurons overexpressing SOD1-G93A to Thimerosal toxicity through SIRT1/DREAM/PDYN pathway.
Neurotoxicology. 2018 Nov 29;:
Authors: Laudati G, Mascolo L, Guida N, Sirabella R, Pizzorusso V, Bruzzaniti S, Serani A, Di Renzo G, Canzoniero LM, Formisano L
Abstract
In humans, mutation of glycine 93 to alanine of Cu++/Zn++ superoxide dismutase type-1 (SOD1-G93 A) has been associated to some familial cases of Amyotrophic Lateral Sclerosis (ALS). Several evidence proposed the involvement of environmental pollutants that like mercury could accelerate ALS symptoms. SH-SY5Y cells stably transfected with SOD1 and G93 A mutant of SOD1 constructs were exposed to non-toxic concentrations (0.01 µM) of ethylmercury thiosalicylate (thimerosal) for 24 hours. Interestingly, we found that thimerosal, in SOD1-G93 A cells, but not in SOD1 cells, reduced cell survival. Furthermore, thimerosal-induced cell death occurred in a concentration dependent-manner and was prevented by the Sirtuin 1 (SIRT1) activator Resveratrol (RSV). Moreover, thimerosal decreased the protein expression of transcription factor Downstream Regulatory Element Antagonist Modulator (DREAM), but not DREAM gene. Interestingly, DREAM reduction was blocked by co-treatment with RSV, suggesting the participation of SIRT1 in determining this effect. Immunoprecipitation experiments in SOD1-G93 A cells expose...

Source: Neurotoxicology - November 29, 2018 Category: Neurology Authors: Laudati G, Mascolo L, Guida N, Sirabella R, Pizzorusso V, Bruzzaniti S, Serani A, Di Renzo G, Canzoniero LM, Formisano L Tags: Neurotoxicology Source Type: research