Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons

Ulrike Kemmerling, Pablo Muñoz, Marioly Müller, Gina Sánchez, María L. Aylwin, Eric Klann, M. Angélica Carrasco, Cecilia Hidalgo

Research output: Contribution to journalArticle

Abstract

Hydrogen peroxide, which stimulates ERK phosphorylation and synaptic plasticity in hippocampal neurons, has also been shown to stimulate calcium release in muscle cells by promoting ryanodine receptor redox modification (S-glutathionylation). We report here that exposure of N2a cells or rat hippocampal neurons in culture to 200 μM H2O2 elicited calcium signals, increased ryanodine receptor S-glutathionylation, and enhanced both ERK and CREB phosphorylation. In mouse hippocampal slices, H2O2 (1 μM) also stimulated ERK and CREB phosphorylation. Preincubation with ryanodine (50 μM) largely prevented the effects of H2O2 on calcium signals and ERK/CREB phosphorylation. In N2a cells, the ERK kinase inhibitor U0126 suppressed ERK phosphorylation and abolished the stimulation of CREB phosphorylation produced by H2O2, suggesting that H2O2 enhanced CREB phosphorylation via ERK activation. In N2a cells in calcium-free media, 200 μM H2O2 stimulated ERK and CREB phosphorylation, while preincubation with thapsigargin prevented these enhancements. These combined results strongly suggest that H2O2 promotes ryanodine receptors redox modification; the resulting calcium release signals, by enhancing ERK activity, would increase CREB phosphorylation. We propose that ryanodine receptor stimulation by activity-generated redox species produces calcium release signals that may contribute significantly to hippocampal synaptic plasticity, including plasticity that requires long-lasting ERK-dependent CREB phosphorylation.

Original languageEnglish (US)
Pages (from-to)491-502
Number of pages12
JournalCell Calcium
Volume41
Issue number5
DOIs
StatePublished - May 2007

Fingerprint

Ryanodine Receptor Calcium Release Channel
Hydrogen Peroxide
Phosphorylation
Calcium
Neurons
Oxidation-Reduction
Neuronal Plasticity
Ryanodine
Thapsigargin
Muscle Cells
Phosphotransferases

Keywords

  • Calcium release channels
  • Hippocampus
  • Intracellular stores
  • Reactive oxygen species
  • Redox modifications
  • S-glutathionylation
  • Synaptic plasticity

ASJC Scopus subject areas

  • Cell Biology
  • Endocrinology

Cite this

Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons. / Kemmerling, Ulrike; Muñoz, Pablo; Müller, Marioly; Sánchez, Gina; Aylwin, María L.; Klann, Eric; Carrasco, M. Angélica; Hidalgo, Cecilia.

In: Cell Calcium, Vol. 41, No. 5, 05.2007, p. 491-502.

Research output: Contribution to journalArticle

Kemmerling, Ulrike ; Muñoz, Pablo ; Müller, Marioly ; Sánchez, Gina ; Aylwin, María L. ; Klann, Eric ; Carrasco, M. Angélica ; Hidalgo, Cecilia. / Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons. In: Cell Calcium. 2007 ; Vol. 41, No. 5. pp. 491-502.
@article{a0fc302ed03f44259894718be53c83b1,
title = "Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons",
abstract = "Hydrogen peroxide, which stimulates ERK phosphorylation and synaptic plasticity in hippocampal neurons, has also been shown to stimulate calcium release in muscle cells by promoting ryanodine receptor redox modification (S-glutathionylation). We report here that exposure of N2a cells or rat hippocampal neurons in culture to 200 μM H2O2 elicited calcium signals, increased ryanodine receptor S-glutathionylation, and enhanced both ERK and CREB phosphorylation. In mouse hippocampal slices, H2O2 (1 μM) also stimulated ERK and CREB phosphorylation. Preincubation with ryanodine (50 μM) largely prevented the effects of H2O2 on calcium signals and ERK/CREB phosphorylation. In N2a cells, the ERK kinase inhibitor U0126 suppressed ERK phosphorylation and abolished the stimulation of CREB phosphorylation produced by H2O2, suggesting that H2O2 enhanced CREB phosphorylation via ERK activation. In N2a cells in calcium-free media, 200 μM H2O2 stimulated ERK and CREB phosphorylation, while preincubation with thapsigargin prevented these enhancements. These combined results strongly suggest that H2O2 promotes ryanodine receptors redox modification; the resulting calcium release signals, by enhancing ERK activity, would increase CREB phosphorylation. We propose that ryanodine receptor stimulation by activity-generated redox species produces calcium release signals that may contribute significantly to hippocampal synaptic plasticity, including plasticity that requires long-lasting ERK-dependent CREB phosphorylation.",
keywords = "Calcium release channels, Hippocampus, Intracellular stores, Reactive oxygen species, Redox modifications, S-glutathionylation, Synaptic plasticity",
author = "Ulrike Kemmerling and Pablo Mu{\~n}oz and Marioly M{\"u}ller and Gina S{\'a}nchez and Aylwin, {Mar{\'i}a L.} and Eric Klann and Carrasco, {M. Ang{\'e}lica} and Cecilia Hidalgo",
year = "2007",
month = "5",
doi = "10.1016/j.ceca.2006.10.001",
language = "English (US)",
volume = "41",
pages = "491--502",
journal = "Cell Calcium",
issn = "0143-4160",
publisher = "Churchill Livingstone",
number = "5",

}

TY - JOUR

T1 - Calcium release by ryanodine receptors mediates hydrogen peroxide-induced activation of ERK and CREB phosphorylation in N2a cells and hippocampal neurons

AU - Kemmerling, Ulrike

AU - Muñoz, Pablo

AU - Müller, Marioly

AU - Sánchez, Gina

AU - Aylwin, María L.

AU - Klann, Eric

AU - Carrasco, M. Angélica

AU - Hidalgo, Cecilia

PY - 2007/5

Y1 - 2007/5

N2 - Hydrogen peroxide, which stimulates ERK phosphorylation and synaptic plasticity in hippocampal neurons, has also been shown to stimulate calcium release in muscle cells by promoting ryanodine receptor redox modification (S-glutathionylation). We report here that exposure of N2a cells or rat hippocampal neurons in culture to 200 μM H2O2 elicited calcium signals, increased ryanodine receptor S-glutathionylation, and enhanced both ERK and CREB phosphorylation. In mouse hippocampal slices, H2O2 (1 μM) also stimulated ERK and CREB phosphorylation. Preincubation with ryanodine (50 μM) largely prevented the effects of H2O2 on calcium signals and ERK/CREB phosphorylation. In N2a cells, the ERK kinase inhibitor U0126 suppressed ERK phosphorylation and abolished the stimulation of CREB phosphorylation produced by H2O2, suggesting that H2O2 enhanced CREB phosphorylation via ERK activation. In N2a cells in calcium-free media, 200 μM H2O2 stimulated ERK and CREB phosphorylation, while preincubation with thapsigargin prevented these enhancements. These combined results strongly suggest that H2O2 promotes ryanodine receptors redox modification; the resulting calcium release signals, by enhancing ERK activity, would increase CREB phosphorylation. We propose that ryanodine receptor stimulation by activity-generated redox species produces calcium release signals that may contribute significantly to hippocampal synaptic plasticity, including plasticity that requires long-lasting ERK-dependent CREB phosphorylation.

AB - Hydrogen peroxide, which stimulates ERK phosphorylation and synaptic plasticity in hippocampal neurons, has also been shown to stimulate calcium release in muscle cells by promoting ryanodine receptor redox modification (S-glutathionylation). We report here that exposure of N2a cells or rat hippocampal neurons in culture to 200 μM H2O2 elicited calcium signals, increased ryanodine receptor S-glutathionylation, and enhanced both ERK and CREB phosphorylation. In mouse hippocampal slices, H2O2 (1 μM) also stimulated ERK and CREB phosphorylation. Preincubation with ryanodine (50 μM) largely prevented the effects of H2O2 on calcium signals and ERK/CREB phosphorylation. In N2a cells, the ERK kinase inhibitor U0126 suppressed ERK phosphorylation and abolished the stimulation of CREB phosphorylation produced by H2O2, suggesting that H2O2 enhanced CREB phosphorylation via ERK activation. In N2a cells in calcium-free media, 200 μM H2O2 stimulated ERK and CREB phosphorylation, while preincubation with thapsigargin prevented these enhancements. These combined results strongly suggest that H2O2 promotes ryanodine receptors redox modification; the resulting calcium release signals, by enhancing ERK activity, would increase CREB phosphorylation. We propose that ryanodine receptor stimulation by activity-generated redox species produces calcium release signals that may contribute significantly to hippocampal synaptic plasticity, including plasticity that requires long-lasting ERK-dependent CREB phosphorylation.

KW - Calcium release channels

KW - Hippocampus

KW - Intracellular stores

KW - Reactive oxygen species

KW - Redox modifications

KW - S-glutathionylation

KW - Synaptic plasticity

UR - http://www.scopus.com/inward/record.url?scp=33947172493&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33947172493&partnerID=8YFLogxK

U2 - 10.1016/j.ceca.2006.10.001

DO - 10.1016/j.ceca.2006.10.001

M3 - Article

C2 - 17074386

AN - SCOPUS:33947172493

VL - 41

SP - 491

EP - 502

JO - Cell Calcium

JF - Cell Calcium

SN - 0143-4160

IS - 5

ER -