| Literature DB >> 18037896 |
John A Muraski1, Marcello Rota, Yu Misao, Jenna Fransioli, Christopher Cottage, Natalie Gude, Grazia Esposito, Francesca Delucchi, Michael Arcarese, Roberto Alvarez, Sailay Siddiqi, Gregory N Emmanuel, Weitao Wu, Kimberlee Fischer, Joshua J Martindale, Christopher C Glembotski, Annarosa Leri, Jan Kajstura, Nancy Magnuson, Anton Berns, Remus M Beretta, Steven R Houser, Erik M Schaefer, Piero Anversa, Mark A Sussman.
Abstract
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.Entities:
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Year: 2007 PMID： 18037896 DOI： 10.1038/nm1671
Source DB: PubMed Journal: Nat Med ISSN： 1078-8956 Impact factor: 53.440