The Shc protein Rai enhances T-cell survival under hypoxia.
Hypoxia occurs in physiological and pathological conditions. T cells experience hypoxia in pathological and physiological conditions as well as in lymphoid organs. Indeed, hypoxia-inducible factor 1α (HIF-1α) affects T cell survival and functions. Rai, an Shc family protein member, exerts pro-survival effects in hypoxic neuroblastoma cells. Since Rai is also expressed in T cells, we here investigated its role in hypoxic T cells. In this work, hypoxia differently affected cell survival, proapoptotic, and metabolic programs in T cells, depending upon Rai expression. By using Jurkat cells stably expressing Rai and splenocytes from Rai-/- mice, we demonstrated that Rai promotes T cell survival and affects cell metabolism under hypoxia. Upon exposure to hypoxia, Jurkat T cells expressing Rai show (a) higher HIF-1α protein levels; (b) a decreased cell death and increased Akt/extracellular-signal-regulated kinase phosphorylation; (c) a decreased expression of proapoptotic markers, including caspase activities and poly(ADP-ribose) polymerase cleavage; (d) an increased glucose and lactate metabolism; (e) an increased activation of nuclear factor-kB pathway. The opposite effects were observed in hypoxic splenocytes from Rai-/- mice. Thus, Rai plays an important role in hypoxic signaling and may be relevant in the protection of T cells against hypoxia.
['Criscuoli|Mattia|M|', 'Ulivieri|Cristina|C|', 'Filippi|Irene|I|', 'Monaci|Sara|S|', 'Guerrini|Giuditta|G|0000-0002-1446-0556', 'Crifò|Bianca|B|', 'De Tommaso|Domiziana|D|', 'Pelicci|Giuliana|G|', 'Baldari|Cosima T|CT|', 'Taylor|Cormac T|CT|', 'Carraro|Fabio|F|', 'Naldini|Antonella|A|0000-0002-9600-2486']
D000818:Animals D017209:Apoptosis D020169:Caspases D015687:Cell Hypoxia D002470:Cell Survival D005947:Glucose D006801:Humans D051795:Hypoxia-Inducible Factor 1, alpha Subunit D019169:Jurkat Cells D019344:Lactic Acid D051379:Mice D018345:Mice, Knockout D009447:Neuroblastoma D010766:Phosphorylation D051057:Proto-Oncogene Proteins c-akt D013601:T-Lymphocytes D015534:Trans-Activators
Shc protein hypoxia T cell HIF-1α cell survival