Effects of microgravity and oxidative stress on human T lymphocytes: different approaches to study their protein expression and post-translational modifications

The aim of this research project was to study the protein expression and post-translational modifications of human T cells exposed to microgravity and oxidative stress. We analysed components of the IL2/IL-2R signalling system and cytoskeletal components known to be negatively affected by microgravity. Little information is available regarding changes in phosphorylation and their functional consequences in T cells subjected to microgravity. This data could be a valuable indicator of microgravity's impact on cellular metabolism. Clinical problems related to disturbed immune cell functions in astronauts during long-term space flights could be anticipated and prevented.Many pathologies seem to be directly or indirectly linked to oxidative phenomena, which influence protein phosphorylation changes. Such changes have been associated with a molecular switch in the pathways that regulate cell proliferation and carcinogenesis.In this thesis, T cell response in extreme conditions was evaluated to better clarify the chemical complexity of the lymphocytic proteome. Particularly, I focused on the Spleen Tyrosine Kinase family components, Syk and Zap-70, already known in the literature for their behaviour in pathological states and for their possible role in the treatment of some forms of leukemia and lymphoma. Western blot analysis of total proteins of T cells treated in different ways showed a strong phosphorylative response and a consistent expression of Syk kinase.