Brief Isoflurane Anesthesia Produces Prominent Phosphoproteomic Changes in the Adult Mouse Hippocampus

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Kohtala , S , Theilmann , W , Suomi , T , Wigren , H-K , Porkka-Heiskanen , T , Elo , L L , Rokka , A & Rantamaki , T 2016 , ' Brief Isoflurane Anesthesia Produces Prominent Phosphoproteomic Changes in the Adult Mouse Hippocampus ' , ACS chemical neuroscience , vol. 7 , no. 6 , pp. 749-756 .

Title: Brief Isoflurane Anesthesia Produces Prominent Phosphoproteomic Changes in the Adult Mouse Hippocampus
Author: Kohtala, Samuel; Theilmann, Wiebke; Suomi, Tomi; Wigren, Henna-Kaisa; Porkka-Heiskanen, Tarja; Elo, Laura L.; Rokka, Anne; Rantamaki, Tomi
Contributor organization: Biosciences
Neuroscience Center
Physiology and Neuroscience (-2020)
Department of Physiology
Laboratory of Neurotherapeutics
Date: 2016-06
Language: eng
Number of pages: 8
Belongs to series: ACS chemical neuroscience
ISSN: 1948-7193
Abstract: Anesthetics are widely used in medical practice and experimental research, yet the neurobiological basis governing their effects remains obscure. We have here used quantitative phosphoproteomics to investigate the protein phosphorylation changes produced by a 30 min isoflurane anesthesia in the adult mouse hippocampus. Altogether 318 phosphorylation alterations in total of 237 proteins between sham and isoflurane anesthesia were identified. Many of the hit proteins represent primary pharmacological targets of anesthetics. However, findings also enlighten the role of several other proteins implicated in various biological processes including neuronal excitability, brain energy homeostasis, synaptic plasticity and transmission, and microtubule function as putative (secondary) targets of anesthetics. In particular, isoflurane increases glycogen synthase kinase-3 beta (GSK3 beta) phosphorylation at the inhibitory Ser(9) residue and regulates the phosphorylation of multiple proteins downstream and upstream of this promiscuous kinase that regulate diverse biological functions. Along with confirmatory Western blot data for GSK3 beta and p44/42-MAPK (mitogen-activated protein kinase; reduced phosphorylation of the activation loop), we observed increased phosphorylation of microtubule-associated protein 2 (MAP2) on residues (Thr(1620,1623)) that have been shown to render its dissociation from microtubules and alterations in microtubule stability. We further demonstrate that diverse anesthetics (sevoflurane, urethane, ketamine) produce essentially similar phosphorylation changes on GSK3 beta, p44/p42-MAPK, and MAP2 as observed with isoflurane. Altogether our study demonstrates the potential of quantitative phosphoproteomics to study the mechanisms of anesthetics (and other drugs) in the mammalian brain and reveals how already a relatively brief anesthesia produces pronounced phosphorylation changes in multiple proteins in the central nervous system.
Subject: Anesthesia
protein phosphorylation
phosphopeptide enrichment
quantitative phosphoproteomics
glycogen synthase kinase-3 beta
3112 Neurosciences
3126 Surgery, anesthesiology, intensive care, radiology
Peer reviewed: Yes
Rights: other
Usage restriction: openAccess
Self-archived version: publishedVersion

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