PMID- 15153095
OWN - NLM
STAT- MEDLINE
DCOM- 20040706
LR  - 20181113
IS  - 0014-2956 (Print)
IS  - 1432-1033 (Electronic)
IS  - 0014-2956 (Linking)
VI  - 271
IP  - 11
DP  - 2004 Jun
TI  - Oxidative neuronal injury. The dark side of ERK1/2.
PG  - 2060-6
AB  - The extracellular signal regulated protein kinases (ERK1/2) are essential for 
      normal development and functional plasticity of the central nervous system. 
      However, a growing number of recent studies in models of cerebral ischemia, brain 
      trauma and neurodegenerative diseases implicate a detrimental role for ERK1/2 
      signaling during oxidative neuronal injury. Neurons undergoing oxidative 
      stress-related injuries typically display a biphasic or sustained pattern of 
      ERK1/2 activation. A variety of potential targets of reactive oxygen species and 
      reactive nitrogen species could contribute to ERK1/2 activation. These include 
      cell surface receptors, G proteins, upstream kinases, protein phosphatases and 
      proteasome components, each of which could be direct or indirect targets of 
      reactive oxygen or nitrogen species, thereby modulating the duration and 
      magnitude of ERK1/2 activation. Neuronal oxidative stress also appears to 
      influence the subcellular trafficking and/or localization of activated ERK1/2. 
      Differences in compartmentalization of phosphorylated ERK1/2 have been observed 
      in diseased or injured human neurons and in their respective animal and cell 
      culture model systems. We propose that differential accessibility of ERK1/2 to 
      downstream targets, which is dictated by the persistent activation of ERK1/2 
      within distinct subcellular compartments, underlies the neurotoxic responses that 
      are driven by this kinase.
FAU - Chu, Charleen T
AU  - Chu CT
AD  - Department of Pathology, Division of Neuropathology, University of Pittsburgh 
      School of Medicine, Room A-516 UPMC Presbyterian, 200 Lothrop Street, Pittsburgh, 
      PA 15213, USA. chu@np.awing.upmc.edu
FAU - Levinthal, David J
AU  - Levinthal DJ
FAU - Kulich, Scott M
AU  - Kulich SM
FAU - Chalovich, Elisabeth M
AU  - Chalovich EM
FAU - DeFranco, Donald B
AU  - DeFranco DB
LA  - eng
GR  - F30 NS 43824/NS/NINDS NIH HHS/United States
GR  - F30 NS043824/NS/NINDS NIH HHS/United States
GR  - R01 NS040817/NS/NINDS NIH HHS/United States
GR  - R01 NS 38319/NS/NINDS NIH HHS/United States
GR  - R01 NS038319/NS/NINDS NIH HHS/United States
GR  - R01 NS 40817/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - England
TA  - Eur J Biochem
JT  - European journal of biochemistry
JID - 0107600
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Neuroprotective Agents)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinase 3)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Brain Ischemia/enzymology
MH  - Cell Death
MH  - Cell Nucleus/enzymology
MH  - Central Nervous System Diseases/enzymology/pathology
MH  - Enzyme Inhibitors/pharmacology
MH  - *MAP Kinase Signaling System
MH  - Mitogen-Activated Protein Kinase 1/analysis/antagonists & inhibitors/*physiology
MH  - Mitogen-Activated Protein Kinase 3
MH  - Mitogen-Activated Protein Kinases/analysis/antagonists & inhibitors/*physiology
MH  - Neurodegenerative Diseases/enzymology
MH  - Neurons/cytology/*enzymology
MH  - Neuroprotective Agents/pharmacology
MH  - Oxidation-Reduction
MH  - *Oxidative Stress
PMC - PMC1899467
MID - NIHMS20816
EDAT- 2004/05/22 05:00
MHDA- 2004/07/09 05:00
PMCR- 2007/06/26
CRDT- 2004/05/22 05:00
PHST- 2004/05/22 05:00 [pubmed]
PHST- 2004/07/09 05:00 [medline]
PHST- 2004/05/22 05:00 [entrez]
PHST- 2007/06/26 00:00 [pmc-release]
AID - EJB4132 [pii]
AID - 10.1111/j.1432-1033.2004.04132.x [doi]
PST - ppublish
SO  - Eur J Biochem. 2004 Jun;271(11):2060-6. doi: 10.1111/j.1432-1033.2004.04132.x.