Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain

Xiaohua Li, Ari B. Friedman, Myoung Sun Roh, Richard S Jope

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with ∼90% dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3.

Original languageEnglish
Pages (from-to)701-704
Number of pages4
JournalJournal of Neurochemistry
Volume92
Issue number3
DOIs
StatePublished - Feb 1 2005
Externally publishedYes

Fingerprint

Glycogen Synthase Kinase 3
Phosphorylation
Serine
Brain
Anesthesia
Anesthetics
Chloral Hydrate
Neuronal Plasticity
Halothane
Pentobarbital
Mood Disorders
Plasticity
Alzheimer Disease
Protein Isoforms

Keywords

  • Anesthesia
  • Glycogen synthase kinase-3
  • Pentobarbital
  • Post-mortem interval

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain. / Li, Xiaohua; Friedman, Ari B.; Roh, Myoung Sun; Jope, Richard S.

In: Journal of Neurochemistry, Vol. 92, No. 3, 01.02.2005, p. 701-704.

Research output: Contribution to journalArticle

@article{1279797aae844d58929b5127166c7a7e,
title = "Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain",
abstract = "Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with ∼90{\%} dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3.",
keywords = "Anesthesia, Glycogen synthase kinase-3, Pentobarbital, Post-mortem interval",
author = "Xiaohua Li and Friedman, {Ari B.} and Roh, {Myoung Sun} and Jope, {Richard S}",
year = "2005",
month = "2",
day = "1",
doi = "10.1111/j.1471-4159.2004.02898.x",
language = "English",
volume = "92",
pages = "701--704",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "3",

}

TY - JOUR

T1 - Anesthesia and post-mortem interval profoundly influence the regulatory serine phosphorylation of glycogen synthase kinase-3 in mouse brain

AU - Li, Xiaohua

AU - Friedman, Ari B.

AU - Roh, Myoung Sun

AU - Jope, Richard S

PY - 2005/2/1

Y1 - 2005/2/1

N2 - Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with ∼90% dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3.

AB - Glycogen synthase kinase-3 (GSK3) is a crucial enzyme contributing to the regulation of neuronal structure, plasticity and survival, is implicated as a contributory factor in prevalent diseases such as Alzheimer's disease and mood disorders and is regulated by a wide range of signaling systems and pharmacological agents. Therefore, factors regulating GSK3 in vivo are currently of much interest. GSK3 is inhibited by phosphorylation of serine-9 or serine-21 in GSK3β and GSK3α, respectively. This study found that accurate measurements of phospho-Ser-GSK3 in brain are confounded by a rapid post-mortem dephosphorylation, with ∼90% dephosphorylation of both GSK3 isoforms occurring within 2 min post-mortem. Furthermore, three anesthetics, pentobarbital, halothane and chloral hydrate, each caused large in vivo increases in the serine phosphorylation of both GSK3β and GSK3α in several regions of mouse brain. Thus, studies of the phosphorylation state of GSK3 in brain, and perhaps in other tissues, need to take into account post-mortem changes and the effects of anesthetics and there is a direct correlation between anesthesia and high levels of serine-phosphorylated GSK3.

KW - Anesthesia

KW - Glycogen synthase kinase-3

KW - Pentobarbital

KW - Post-mortem interval

UR - http://www.scopus.com/inward/record.url?scp=13244253861&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=13244253861&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2004.02898.x

DO - 10.1111/j.1471-4159.2004.02898.x

M3 - Article

C2 - 15659239

AN - SCOPUS:13244253861

VL - 92

SP - 701

EP - 704

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 3

ER -