Chapter

Brain Edema XII

Volume 86 of the series Acta Neurochirurgica Supplements pp 227-230

Akt phosphorylation and cell survival after hypoxia-induced cytochrome c release in superfused respiring neonatal rat cerebrocortical slices

  • K. HiraiAffiliated withDepartment of Anesthesia, University of California, San Francisco
  • , T. HayashiAffiliated withDepartments of Neurosurgery, Neurology and Neurological Sciences, and Program in Neurosciences, Stanford University School of Medicine
  • , P. H. ChanAffiliated withDepartment of Anesthesia, University of California, San Francisco
  • , V. J. BasusAffiliated withDepartment of Pharmaceutical Chemistry, University of California, San Francisco
  • , T. L. JamesAffiliated withDepartment of Pharmaceutical Chemistry, University of California, San Francisco
  • , Lawrence LittAffiliated withDepartment of Anesthesia, University of California, San Francisco

* Final gross prices may vary according to local VAT.

Get Access

Abstract

Phosphorylation of Akt before hypoxia (30 min) and during reoxygenation (4 h) was evaluated in superperfused neonatal rat cerebrocortical slices (350 μm, P7, Sprague-Dawley). Cytosolic cytochrome c intensities in Western blots, which were increased at the end of hypoxia, were decreased during reoxygenation. Western blot intensities of phosphorylated Akt (phospho-Akt), nearly undetectable at the end of hypoxia, recovered quickly during reoxygenation, in a trend opposite that for cytochrome c. At 1.5 h and 4 h after hypoxia they became larger or the same as before hypoxia. Total Akt was unchanged by hypoxia and reoxygenation. Phosphocreatine (PCr) and nucleotide triphosphates (NTP) were measured in parallel 14.1 Tesla ex vivo 31P NMR superfused brain slice studies. PCr and α-NTP were nearly undetectable at the end of hypoxia. Although they recovered quickly after hypoxia, they were lower than before hypoxia. Reductions in phospho-Akt during hypoxia were consistent with the general unavailability of basic high energy phosphates. Preferential phosphorylation of Akt after hypoxia suggested that substantial reductions in intracellular energy, as indicated by PCr and NTP, might be tolerated by processes important for generating phospho-Akt. Additionally, the post-hypoxia increase in phospho-Akt might have contributed to concomitant reductions in cytosolic cytochrome c.

Akt brain slice cytochrome c hypoxia NMR (nuclear magnetic resonance) NTP (nucleotide triphosphates) phosphorylation