AIM: The aim of this study was to investigate the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), glycogen synthase kinase-3beta (GSK3-beta) and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which are the components of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and expression of S-phase kinase-associated protein 2 (Skp2) messenger RNA (mRNA) in renal ischemia/reperfusion. MATERIALS AND METHODS: Three experimental groups, sham-operative mice, vehicle-delivered mice and wortmannin-treated ischemia/reperfusion injury (IRI) mice were designed to examine PDK1, GSK3-beta and PTEN phosphorylation status, as well as expression of Skp2 mRNA at 30 min, 90 min, 24 h and 48 h of reperfusion after ischemia treatment. Wortmannin or its vehicle was given intraperitoneally 4 h before surgery. Expression of Skp2 mRNA was examined by semiquantitative reverse-transcription PCR, and the components of the PI3K/Akt pathway were detected by western blotting in the IRI kidney. RESULTS: Phosphorylation of PDK1(Ser241), GSK3-beta(Ser9) and PTEN(Ser380) was increased after ischemia/reperfusion in the mouse kidney, and phosphorylation of PDK1 was reduced by wortmannin administration. The renal Skp2 mRNA increased after IRI in mouse, which could be inhibited by wortmannin. CONCLUSIONS: Our primary study suggests that the PI3K/Akt signaling pathway plays an important role in regulating the repair following renal IRI. The Skp2 mRNA increased in the IRI kidney and may be regulated by the PI3K/Akt pathway.
AIM: The aim of this study was to investigate the role of 3-phosphoinositide-dependent protein kinase-1 (PDK1), glycogen synthase kinase-3beta (GSK3-beta) and phosphatase and tensin homologue deleted on chromosome 10 (PTEN), which are the components of the phosphoinositide 3-kinase (PI3K)/Akt pathway, and expression of S-phase kinase-associated protein 2 (Skp2) messenger RNA (mRNA) in renal ischemia/reperfusion. MATERIALS AND METHODS: Three experimental groups, sham-operative mice, vehicle-delivered mice and wortmannin-treated ischemia/reperfusion injury (IRI) mice were designed to examine PDK1, GSK3-beta and PTEN phosphorylation status, as well as expression of Skp2 mRNA at 30 min, 90 min, 24 h and 48 h of reperfusion after ischemia treatment. Wortmannin or its vehicle was given intraperitoneally 4 h before surgery. Expression of Skp2 mRNA was examined by semiquantitative reverse-transcription PCR, and the components of the PI3K/Akt pathway were detected by western blotting in the IRI kidney. RESULTS: Phosphorylation of PDK1(Ser241), GSK3-beta(Ser9) and PTEN(Ser380) was increased after ischemia/reperfusion in the mouse kidney, and phosphorylation of PDK1 was reduced by wortmannin administration. The renal Skp2 mRNA increased after IRI in mouse, which could be inhibited by wortmannin. CONCLUSIONS: Our primary study suggests that the PI3K/Akt signaling pathway plays an important role in regulating the repair following renal IRI. The Skp2 mRNA increased in the IRI kidney and may be regulated by the PI3K/Akt pathway.
Authors: B A Schulman; A C Carrano; P D Jeffrey; Z Bowen; E R Kinnucan; M S Finnin; S J Elledge; J W Harper; M Pagano; N P Pavletich Journal: Nature Date: 2000-11-16 Impact factor: 49.962
Authors: N Omori; G Jin; F Li; W R Zhang; S J Wang; Y Hamakawa; I Nagano; Y Manabe; M Shoji; K Abe Journal: Brain Res Date: 2002-11-08 Impact factor: 3.252
Authors: Kelly D Smith; Lucile E Wrenshall; Roberto F Nicosia; Raimund Pichler; Christopher L Marsh; Charles E Alpers; Nayak Polissar; Connie L Davis Journal: J Am Soc Nephrol Date: 2003-04 Impact factor: 10.121