NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1

Kenneth T. Kishida, Maryland Pao, Steven M. Holland, Eric Klann

Research output: Contribution to journalArticle

Abstract

Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1.

Original languageEnglish (US)
Pages (from-to)299-306
Number of pages8
JournalJournal of Neurochemistry
Volume94
Issue number2
DOIs
StatePublished - Jul 2005

Fingerprint

NADPH Oxidase
Extracellular Signal-Regulated MAP Kinases
N-Methyl-D-Aspartate Receptors
Chemical activation
Reactive Oxygen Species
Scavenging
Superoxides
Catalase
Superoxide Dismutase
Antioxidants
Acetylcysteine
N-Methylaspartate
Enzymes
Hydrogen Peroxide
Membranes
Proteins

Keywords

  • Learning and memory
  • Long-term potentiation
  • Oxygen species
  • Reactive
  • Superoxide

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. / Kishida, Kenneth T.; Pao, Maryland; Holland, Steven M.; Klann, Eric.

In: Journal of Neurochemistry, Vol. 94, No. 2, 07.2005, p. 299-306.

Research output: Contribution to journalArticle

Kishida, Kenneth T. ; Pao, Maryland ; Holland, Steven M. ; Klann, Eric. / NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. In: Journal of Neurochemistry. 2005 ; Vol. 94, No. 2. pp. 299-306.
@article{a53abee0e9d94f2ca2b81578b8066383,
title = "NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1",
abstract = "Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1.",
keywords = "Learning and memory, Long-term potentiation, Oxygen species, Reactive, Superoxide",
author = "Kishida, {Kenneth T.} and Maryland Pao and Holland, {Steven M.} and Eric Klann",
year = "2005",
month = "7",
doi = "10.1111/j.1471-4159.2005.03189.x",
language = "English (US)",
volume = "94",
pages = "299--306",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1

AU - Kishida, Kenneth T.

AU - Pao, Maryland

AU - Holland, Steven M.

AU - Klann, Eric

PY - 2005/7

Y1 - 2005/7

N2 - Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1.

AB - Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47phox, one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1.

KW - Learning and memory

KW - Long-term potentiation

KW - Oxygen species

KW - Reactive

KW - Superoxide

UR - http://www.scopus.com/inward/record.url?scp=22244487284&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=22244487284&partnerID=8YFLogxK

U2 - 10.1111/j.1471-4159.2005.03189.x

DO - 10.1111/j.1471-4159.2005.03189.x

M3 - Article

C2 - 15998281

AN - SCOPUS:22244487284

VL - 94

SP - 299

EP - 306

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -