title: Effect of persistent activation of phosphoinositide 3-kinase on heart.
abstract: OBJECTIVE
  Insulin/insulin-like growth factor-1 (IGF-1) signaling plays an important role in many biological processes. The class IA isoform of phosphoinositide 3-kinase (PI3K) is an important downstream effector of the insulin/IGF-1 signaling pathway. The aim of this study is to examine the effect of persistent activation of PI3K on gene expression and markers of cellular senescence in murine hearts.
  
  
  METHODS
  Transgenic mice expressing a constitutively active PI3K in a heart-specific manner were analyzed at the ages of 3 and 20 months. Effects of persistent activation of PI3K on gene expression were comprehensively analyzed using microarrays.
  
  
  RESULTS
  Upon comprehensive gene expression profiling, the genes whose expression was increased included those for several heat shock chaperons. The amount and nuclear localization of a forkhead box O (FOXO) protein was increased. In addition, the gene expression of insulin receptor substrate-2 decreased, and that of phosphatase and tensin homolog deleted on chromosome ten (PTEN) increased, suggesting that the persistent activation of PI3K modified the expression of molecules of insulin/IGF-1 signaling. The expression of markers of cellular senescence, such as senescence-associated beta-galactosidase activity, cell cycle inhibitors, proinflammatory cytokines, and lipofuscin, did not differ between old wild-type and caPI3K mice.
  
  
  CONCLUSIONS
  The persistent activation of PI3K modified the expression of molecules of insulin/IGF-1 signaling pathway in a transgenic mouse line. Markers of cellular senescence were not changed in the aged mutant mice.
authors.affiliation: Department of Cardiovascular Medicine, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Niizuma
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Inuzuka
authors.forename: Junji
authors.initials: J
authors.lastname: Okuda
authors.forename: Takao
authors.initials: T
authors.lastname: Kato
authors.forename: Tsuneaki
authors.initials: T
authors.lastname: Kawashima
authors.forename: Yodo
authors.initials: Y
authors.lastname: Tamaki
authors.forename: Yoshitaka
authors.initials: Y
authors.lastname: Iwanaga
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Rie
authors.initials: R
authors.lastname: Kosugi
authors.forename: Kayo
authors.initials: K
authors.lastname: Watanabe-Maeda
authors.forename: Yoji
authors.initials: Y
authors.lastname: Machida
authors.forename: Shingo
authors.initials: S
authors.lastname: Tsuji
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tohru
authors.initials: T
authors.lastname: Izumi
authors.forename: Toru
authors.initials: T
authors.lastname: Kita
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Shioi
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D016922:Cellular Senescence / Q000502:physiology*; D004452:Echocardiography; D004789:Enzyme Activation / Q000502:physiology; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046228:Microarray Analysis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D020123:Sirolimus
chemical_list: D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D020123:Sirolimus