The Shc protein Rai enhances T-cell survival under hypoxia

Mattia Criscuoli, Cristina Ulivieri, Irene Filippi, Sara Monaci, Giuditta Guerrini, Bianca Crifò, Domiziana De Tommaso, Giuliana Pelicci, Cosima T. Baldari, Cormac T. Taylor, Fabio Carraro, Antonella Naldini

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Cellular Physiology
DOIs
Publication statusAccepted/In press - Jan 1 2020

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Keywords

  • cell survival
  • HIF-1α
  • hypoxia
  • Shc protein
  • T cell

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Criscuoli, M., Ulivieri, C., Filippi, I., Monaci, S., Guerrini, G., Crifò, B., De Tommaso, D., Pelicci, G., Baldari, C. T., Taylor, C. T., Carraro, F., & Naldini, A. (Accepted/In press). The Shc protein Rai enhances T-cell survival under hypoxia. Journal of Cellular Physiology. https://doi.org/10.1002/jcp.29461