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The Shc protein Rai enhances T‐cell survival under hypoxia
Author(s) -
Criscuoli Mattia,
Ulivieri Cristina,
Filippi Irene,
Monaci Sara,
Guerrini Giuditta,
Crifò Bianca,
De Tommaso Domiziana,
Pelicci Giuliana,
Baldari Cosima T.,
Taylor Cormac T.,
Carraro Fabio,
Naldini Antonella
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29461
Subject(s) - jurkat cells , hypoxia (environmental) , biology , apoptosis , microbiology and biotechnology , protein kinase b , extracellular , t cell , signal transduction , cancer research , immunology , chemistry , biochemistry , immune system , oxygen , organic chemistry
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.