An in vitro study on protective effect of growth factors on tissue transglutaminase overexpression induced by ?-amyloid in Olfactory Ensheathing Cells.

Tissue transglutaminase (TG2) is a calcium dependent protein implicated in numerous physiological and pathological cellular processes, including some neurodegenerative diseases, such as Alzheimer disease (AD). TG2 activity has been detected in normal and AD brains and it is involved in development of abnormal insoluble neurofilaments. Furthermore, it has been demonstrated that Amyloid-beta (A?) is a substrate for TG2, which is a reactive acceptor and donor sites responsible for the TG-catalysed formation of polymers. In previous studies, we demonstrated a relationship between TG2 and Growth Factors (GFs) in a particular glial cell type, Olfactory Ensheathing Cells (OECs). Specifically, we showed that TG2 overexpression induced by some stressors was down-regulated by GFs exposure in OECs. To monitor cell viability, MTT test was used, while TG2 expression was examined by immunocytochemical and Western Blot analysis. We also considered the involvement of the apoptotic pathway-TG2 mediated. Vimentin expression was also evaluated. We found that in OECs exposed to A? for 24 h, TG2 expression increased, and we observed that the protein appeared prevalently localized in the cytosol. The pre-treatment with GFs down-regulated the TG2 level, which was prevalently limited into the nuclear compartment. Vimentin expression and Caspase cleavage showed a significant enhance in A? exposed cells. The pre-treatment with GFs was able to restore the levels of the proteins to control values, and the intracellular oxidative status modified by the exposure to A?. Our data suggest that GFs could be an innovative mechanism to contrast TG2 expression, which plays a key role in AD.