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Titolo: Stress granules induced by oxidative stress in cultured fibroblast from TDP-43 mutant ALS patients
Data di pubblicazione: 2013
Citazione: Stress granules induced by oxidative stress in cultured fibroblast from TDP-43 mutant ALS patients / Brancia C; Coni P; Floris A; Bellini I; Orrù S; Sogos V. - 118:2(2013), pp. 34-34. ((Intervento presentato al convegno 67° CONGRESSO NAZIONALE SIAI tenutosi a Brescia nel 20-22 settembre 2013.
Abstract: Stress granules (SGs) are transient cytoplasmic aggregates that rapidly form when cells are exposed to stress and consist of large messenger ribonucleoprotein (mRNPs) complexes. The SGs seem to function as storage depots for translation silenced com- plex and are implicated in stress-induced inhibition of global protein synthesis. Protein aggregation, has been observed in several neurodegenerative diseases, including Amyotrophic Lateral Sclerosis (ALS). The protein TDP-43 (TAR DNA-Bind- ing Protein-43), encoded by one of the ALS-causative gene (TARDBP), is a major con- stituent of pathological inclusions in this disease and it is seems to be implicated in the regulation of SGs. Therefore we investigated the different characteristics of SGs in human cultured fibroblasts from ALS patients carrying TARDBPA382T mutation (group 1) versus healthy subjects (group 2). The cells were exposed to stressful conditions using sodium arsenite (SA) at different concentrations (0.5 mM, 1 mM) and exposure times (30 min, 1h). Preliminary results showed, after 30 minutes, small and sporadic cytoplasmic inclusions immunostained for TIA-1(T-cell internal antigen-1), an early marker for SGs, in both groups of cells. After 1h, the TIA-1 immunostained granules were bright, copious and scattered into the cytosol. Interestingly, we observed a sig- nificantly higher number of cells exhibiting SGs in fibroblasts from healthy controls (66%) compared to ALS patients (34%). In parallel, we identified the RNA binding protein HuR-1 (Human antigen R) in a fraction of Tia-1 positive SGs, as well as TDP- 43 localized into the nucleus of all the cells. These data raise the possibility that TDP-43 may modulate the stress granule for- mation, contributing to the cellular response to acute stress. Moreover the TDP-43 may regulate gene expression as well as cellular recovery and survival, and conse- quently its mutation may contribute to the neurodegeneration.
Tipologia:4.2 Abstract in Atti di convegno

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