The role of phosphatidylinositol-3 kinase isomers in myocardial ischemic preconditioning.
Published: 2005
Language: eng
Number of pages: 113
Description: Ischemic preconditioning (IPC) is a novel cell protection mechanism whereby brief periods of sublethal ischemia can protect the myocyte from prolonged ischemia-induced-injury. Recently, several papers suggested that phosphatidylinositol-3 kinase (PI3K) plays an important role in IPC protection. Our study examined the isoform specificity of PI3K in IPC using PI3Kgamma knockout (PI3Kgamma-/-) and PI3Kalpha dominant-negative (PI3KalphaDN) mice. Recovery rate in IPC group was significantly higher than I/R group in wild type hearts. However, the protective effect of IPC was completely abolished in PI3Kgamma-/- hearts. Surprisingly, PI3KalphaDN hearts showed significant recovery after both I/R and IPC. Therefore our studies suggested that PI3Kgamma isomer is involved in IPC and genetic inhibition of PI3Kalpha is resistant against ischemia. Furthermore, examining downstream of PI3K revealed that PI3Kgamma-PKB/Akt-GSK3beta signaling cascade is critical for regulating cell survival. Selective inhibition PI3Kalpha or activation of PI3Kalpha may be novel therapeutic strategies for protecting the ischemic myocardium.
Notes: Source: Masters Abstracts International, Volume: 44-02, page: 0732.

Thesis (M.Sc.)--University of Toronto, 2005.

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