| First Author | Criscuoli M | Year | 2020 |
| Journal | J Cell Physiol | Volume | 235 |
| Issue | 11 | Pages | 8058-8070 |
| PubMed ID | 31944299 | Mgi Jnum | J:304113 |
| Mgi Id | MGI:6694642 | Doi | 10.1002/jcp.29461 |
| Citation | Criscuoli M, et al. (2020) The Shc protein Rai enhances T-cell survival under hypoxia. J Cell Physiol 235(11):8058-8070 |
| abstractText | 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 1alpha (HIF-1alpha) 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-1alpha 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. |
