The Akt1 isoform is an essential mediator of ischaemic preconditioning.
Bottom Line: Phosphatidyl-inositol-3-kinase (PI3K)-Akt pathway is essential for conferring cardioprotection in response to ischaemic preconditioning (IPC) stimulus.However, the role of the individual Akt isoforms expressed in the heart in mediating the protective response to IPC is unknown.Akt1 but not Akt2 is essential for mediating a protective response to an IPC stimulus.
Affiliation: The Hatter Cardiovascular Institute, The Institute of Cardiovascular Science, University College London, London, UK.Show MeSH
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Mentions: Downstream of Akt we studied the phosphorylation of GSK-3β as well as the pro-apoptotic protein, BAD, in response to IPC. We found that GSK-3β phosphorylation was significantly reduced in response to IPC in the Akt1−/− compared to Akt1+/+ mice (0.017 ± 0.0009 versus 0.034 ± 0.002, n = 4, P = 0.0002, Fig. 5A) whereas the total levels of GSK-3β remain the same (Fig. 5B). Preconditioning did not result in increased phosphorylation of BAD in the control Akt1+/+ mice (0.023 ± 0.007 with IPC versus 0.025 ± 0.004 in control, n = 4, Fig. 5C). However, there was a significant decrease in basal-level phosphorylation of BAD in the Akt1−/− compared to Akt1+/+ hearts (0.009 ± 0.003 versus 0.025 ± 0.004, n = 4, P = 0.016, Fig. 5C). Interestingly, the total level of BAD protein was significantly lower in the Akt1−/− hearts compared to Akt1+/+ hearts (0.015 ± 0.002 versus 0.033 ± 0.004, n = 8, P = 0.002, Fig. 5D).
Affiliation: The Hatter Cardiovascular Institute, The Institute of Cardiovascular Science, University College London, London, UK.