| First Author | Muraski JA | Year | 2007 |
| Journal | Nat Med | Volume | 13 |
| Issue | 12 | Pages | 1467-75 |
| PubMed ID | 18037896 | Mgi Jnum | J:130400 |
| Mgi Id | MGI:3771639 | Doi | 10.1038/nm1671 |
| Citation | Muraski JA, et al. (2007) Pim-1 regulates cardiomyocyte survival downstream of Akt. Nat Med 13(12):1467-75 |
| abstractText | The serine-threonine kinases Pim-1 and Akt regulate cellular proliferation and survival. Although Akt is known to be a crucial signaling protein in the myocardium, the role of Pim-1 has been overlooked. Pim-1 expression in the myocardium of mice decreased during postnatal development, re-emerged after acute pathological injury in mice and was increased in failing hearts of both mice and humans. Cardioprotective stimuli associated with Akt activation induced Pim-1 expression, but compensatory increases in Akt abundance and phosphorylation after pathological injury by infarction or pressure overload did not protect the myocardium in Pim-1-deficient mice. Transgenic expression of Pim-1 in the myocardium protected mice from infarction injury, and Pim-1 expression inhibited cardiomyocyte apoptosis with concomitant increases in Bcl-2 and Bcl-X(L) protein levels, as well as in Bad phosphorylation levels. Relative to nontransgenic controls, calcium dynamics were significantly enhanced in Pim-1-overexpressing transgenic hearts, associated with increased expression of SERCA2a, and were depressed in Pim-1-deficient hearts. Collectively, these data suggest that Pim-1 is a crucial facet of cardioprotection downstream of Akt. |
