Access
To read this story in full you will need to login or make a payment (see right).
Article
Nature Medicine 13, 1467 - 1475 (2007)
Published online: 25 November 2007 | doi:10.1038/nm1671
There is a Corrigendum (March 2008) associated with this Article.
Pim-1 regulates cardiomyocyte survival downstream of Akt
John A Muraski1, Marcello Rota2, Yu Misao2, Jenna Fransioli1, Christopher Cottage1, Natalie Gude1, Grazia Esposito2, Francesca Delucchi2, Michael Arcarese2, Roberto Alvarez1, Sailay Siddiqi1, Gregory N Emmanuel1, Weitao Wu1, Kimberlee Fischer1, Joshua J Martindale1, Christopher C Glembotski1, Annarosa Leri2, Jan Kajstura2, Nancy Magnuson3, Anton Berns4, Remus M Beretta5, Steven R Houser5, Erik M Schaefer6, Piero Anversa2 & Mark A Sussman1
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-XL 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.
To read this story in full you will need to login or make a payment (see right).
MORE ARTICLES LIKE THIS
These links to content published by NPG are automatically generated.
RESEARCH
BOB.1/OBF.1 controls the balance of TH1 and TH2 immune responsesThe EMBO Journal Article (11 Jul 2007)
Identification of the prosurvival activity of nerve growth factor on cardiac myocytesCell Death and Differentiation Original Article
Identification of the prosurvival activity of nerve growth factor on cardiac myocytesCell Death and Differentiation Original Article
Small proline-rich protein 1A is a gp130 pathway- and stress-inducible cardioprotective proteinThe EMBO Journal Article (10 Nov 2004)
See all 15 matches for Research