Activation of brain protein phosphatase-1I following cardiac arrest and resuscitation involving an interaction with 14-3-3γ Academic Article uri icon

Overview

MeSH Major

  • 14-3-3 Proteins
  • Brain
  • Heart Arrest
  • Protein Phosphatase 1
  • Resuscitation

abstract

  • The intracellular signaling mechanisms that couple transient cerebral ischemia to cell death and neuroprotective mechanisms provide potential therapeutic targets for cardiac arrest. Protein phosphatase (PP)-1 is a major serine/threonine phosphatase that interacts with and dephosphorylates critical regulators of energy metabolism, ionic balance, and apoptosis. We report here that PP-1(I), a major regulated form of PP-1, is activated in brain by approximately twofold in vivo following cardiac arrest and resuscitation in a clinically relevant pig model of transient global cerebral ischemia and reperfusion. PP-1(I) purified to near homogeneity from either control or ischemic pig brain consisted of the PP-1 catalytic subunit, the inhibitor-2 regulatory subunit, as well as the novel constituents 14-3-3gamma, Rab GDP dissociation protein beta, PFTAIRE kinase, and C-TAK1 kinase. PP-1(I) purified from ischemic brain contained significantly less 14-3-3gamma than PP-1(I) purified from control brain, and purified 14-3-3gamma directly inhibited the catalytic subunit of PP-1 and reconstituted PP-1(I). These findings suggest that activation of brain PP-1(I) following global cerebral ischemia in vivo involves dissociation of 14-3-3gamma, a novel inhibitory modulator of PP-1(I). This identifies modulation of PP-1(I) by 14-3-3 in global cerebral ischemia as a potential signaling mechanism-based approach to neuroprotection.

publication date

  • June 2008

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3872065

Digital Object Identifier (DOI)

  • 10.1111/j.1471-4159.2008.05300.x

PubMed ID

  • 18284617

Additional Document Info

start page

  • 2029

end page

  • 38

volume

  • 105

number

  • 5