Involvement of Akt in preconditioning-induced tolerance to ischemia in PC12 cells

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Joëlle A HillionJohn M Hallenbeck

Abstract

The serine-threonine protein kinase Akt has been identified as an important mediator of cell survival able to counteract apoptotic stimuli. However, hibernation, a model of natural tolerance to cerebral ischemia, is associated with downregulation of Akt. We previously established a model of ischemic tolerance in a PC12 cell line and using this model we now addressed the question whether ischemic tolerance also downregulates Akt in PC12 cells. Kinetic studies showed decreased Akt phosphorylation in tolerized cells. Similarly, phosphorylated levels of three major targets of Akt and well-known proapoptotic factors, the glycogen synthase kinase 3 (GSK-3), a Forkhead family member, FoxO4, and the protein murine double minute 2 (MDM2), all inactivated upon phosphorylation by Akt, were decreased in preconditioned cells. In addition, pharmacological blockade of the phosphoinositide 3-kinase (PI3K)/Akt pathway reduced cell death induced by oxygen and glucose deprivation (OGD) and increased the protective effect of preconditioning (PC). Furthermore, decreasing availability of P-Akt by transfecting PC12 cells with constructs of inactive Akt also resulted in protection against OGD and potentiation of the protective effect of PC. Depending ...Continue Reading

References

Sep 25, 1997·Trends in Biochemical Sciences·B M Marte, J Downward
Feb 20, 1998·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·K U Frerichs, J M Hallenbeck
Jun 8, 1999·The Journal of Biological Chemistry·G RenaP Cohen
Dec 2, 1999·Experimental Cell Research·E S Kandel, N Hay
Mar 31, 2000·Experimental Cell Research·T G CrossJ M Lord
Sep 20, 2000·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·S NamuraA Alessandrini
Mar 21, 2001·Cellular Signalling·D Beitner-JohnsonD E Millhorn
Oct 5, 2001·Nature Reviews. Molecular Cell Biology·P Cohen, S Frame
Mar 30, 2002·The Journal of Biological Chemistry·Yoko OgawaraYukiko Gotoh
Jun 11, 2002·Journal of Molecular and Cellular Cardiology·Mihaela M MocanuDerek M Yellon
Jul 13, 2002·Trends in Biochemical Sciences·Boudewijn M T Burgering, Geert J P L Kops
Jul 26, 2002·Archives of Biochemistry and Biophysics·Karen C Arden, William H Biggs
Sep 20, 2002·Nature·Geert J P L KopsBoudewijn M T Burgering
Jun 28, 2003·FEBS Letters·Michael P Scheid, James R Woodgett
Dec 10, 2003·Oncogene·Thomas F FrankeChizuru Sugimoto
Feb 14, 2004·Cardiovascular Research·Stephen C Armstrong
Apr 17, 2004·Molecular Endocrinology·Melissa A CunninghamJames M Hammond
Apr 23, 2004·Trends in Biochemical Sciences·Richard S Jope, Gail V W Johnson
May 8, 2004·Trends in Biochemical Sciences·Derek P BrazilBrian A Hemmings
Jun 1, 2004·The Journal of Biological Chemistry·Jianhua FengBrian A Hemmings
Jun 10, 2004·The Journal of Veterinary Medical Science·Takayuki NakajimaKoichi Kawahara
Sep 14, 2004·Gastroenterology·Rita CariniEmanuele Albano
Jan 14, 2005·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Joëlle A HillionJohn M Hallenbeck

❮ Previous
Next ❯

Citations

Apr 8, 2009·Nature Neuroscience·Takahiro MiyawakiR Suzanne Zukin
Jun 13, 2012·Proceedings of the National Academy of Sciences of the United States of America·Hakryul JoHongbo R Luo
Nov 15, 2011·Pancreas·Takaharu SaitoMitsukazu Gotoh
Jul 24, 2010·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Wen-Ping GuoJian-Zhong Wu
Dec 6, 2014·FEBS Letters·Ruslan I Dmitriev, Dmitri B Papkovsky
Apr 22, 2009·Biochemical and Biophysical Research Communications·Kiyoshi KikuchiIkuro Maruyama
Sep 21, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Giuseppe PignataroRoger P Simon
Apr 12, 2008·Neuropharmacology·Ulrich Dirnagl, Andreas Meisel
Apr 16, 2008·Brain Research·DaJoie R CroslanByron D Ford
Feb 9, 2008·Journal of the Neurological Sciences·Jun LiLouise D McCullough
Jun 26, 2007·Experimental Eye Research·Hani Levkovitch-VerbinShlomo Melamed
Apr 21, 2012·Biochemical and Biophysical Research Communications·Heng-ai ZhangGuan-hua Du
Dec 17, 2008·Experimental Eye Research·John C DreixlerSteven Roth
Aug 3, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Laura García-PupoRené Delgado-Hernández
Mar 6, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Yunhong ZhangJeffrey M Gidday
Jan 16, 2008·Physiological Reviews·Tihomir Paul Obrenovitch

❮ Previous
Next ❯

Methods Mentioned

BETA
Assay
electrophoresis
transfection
flow cytometry
fluorescence-activated cell sorter
ubiquitination

Software Mentioned

Cell Quest Acquisition and Analysis
GraphPad Prism

Related Concepts

Related Feeds

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.

AKT Pathway

This feed focuses on the AKT serine/threonine kinase, which is an important signaling pathway involved in processes such as glucose metabolism and cell survival.