Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells

Richard S Jope, Liang Zhang, Ling Song

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Although peroxynitrite appears to contribute to neuronal dysfunction in several neurodegenerative disorders, little is known about how peroxynitrite affects cellular signaling processes. This study investigated if peroxynitrite affects the mitogen-activated protein kinases, extracellular- regulated kinases 1 and 2 (ERK1/2) and p38. Exposure of PC12 cells to 500 μM peroxynitrite activated ERK1/2 and 938 within 5 min and this was followed by gradual decreases in activation over the next 25 min. Activation of ERK1/2 by peroxynitrite was mediated by activation of the epidermal growth factor (EGF) receptor in a calcium/calmodulin-dependent kinase II- and src family tyrosine kinase-dependent manner, as it was blocked by the selective EGF receptor inhibitor AG1478, by KN62, an inhibitor of calcium/calmodulin-dependent kinase II, and by PP1, a src family tyrosine kinase inhibitor. Activation of p38 by peroxynitrite was independent of the EGF receptor, required activation of calcium/calmodulin-dependent kinase II and src family tyrosine kinases, and was modulated by nerve growth factor (NGF) in a time-dependent manner. Pretreatment with NGF (2 h) attenuated, whereas cotreatment with NGF potentiated, peroxynitrite-induced activation of p38. Thus, peroxynitrite activates ERK1/2 and p38, activation of EGF receptors, calcium/calmodulin- dependent kinase II, and src family tyrosine kinases participate in these signaling responses to peroxynitrite, and peroxynitrite- and NGF-induced signaling activities converge on p38. (C) 2000 Academic Press.

Original languageEnglish
Pages (from-to)365-370
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume376
Issue number2
DOIs
StatePublished - Apr 15 2000
Externally publishedYes

Fingerprint

Peroxynitrous Acid
PC12 Cells
Phosphotransferases
Chemical activation
Calcium-Calmodulin-Dependent Protein Kinases
src-Family Kinases
Calmodulin
Nerve Growth Factor
Epidermal Growth Factor Receptor
Calcium
Cell signaling
Neurotrophin 3
Mitogen-Activated Protein Kinases
Neurodegenerative Diseases

Keywords

  • Alzheimer's disease
  • ERK
  • NGF
  • Oxidative stress
  • P38
  • Peroxynitrite

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells. / Jope, Richard S; Zhang, Liang; Song, Ling.

In: Archives of Biochemistry and Biophysics, Vol. 376, No. 2, 15.04.2000, p. 365-370.

Research output: Contribution to journalArticle

@article{89038dbf237142d5a36e7366e162ff1f,
title = "Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells",
abstract = "Although peroxynitrite appears to contribute to neuronal dysfunction in several neurodegenerative disorders, little is known about how peroxynitrite affects cellular signaling processes. This study investigated if peroxynitrite affects the mitogen-activated protein kinases, extracellular- regulated kinases 1 and 2 (ERK1/2) and p38. Exposure of PC12 cells to 500 μM peroxynitrite activated ERK1/2 and 938 within 5 min and this was followed by gradual decreases in activation over the next 25 min. Activation of ERK1/2 by peroxynitrite was mediated by activation of the epidermal growth factor (EGF) receptor in a calcium/calmodulin-dependent kinase II- and src family tyrosine kinase-dependent manner, as it was blocked by the selective EGF receptor inhibitor AG1478, by KN62, an inhibitor of calcium/calmodulin-dependent kinase II, and by PP1, a src family tyrosine kinase inhibitor. Activation of p38 by peroxynitrite was independent of the EGF receptor, required activation of calcium/calmodulin-dependent kinase II and src family tyrosine kinases, and was modulated by nerve growth factor (NGF) in a time-dependent manner. Pretreatment with NGF (2 h) attenuated, whereas cotreatment with NGF potentiated, peroxynitrite-induced activation of p38. Thus, peroxynitrite activates ERK1/2 and p38, activation of EGF receptors, calcium/calmodulin- dependent kinase II, and src family tyrosine kinases participate in these signaling responses to peroxynitrite, and peroxynitrite- and NGF-induced signaling activities converge on p38. (C) 2000 Academic Press.",
keywords = "Alzheimer's disease, ERK, NGF, Oxidative stress, P38, Peroxynitrite",
author = "Jope, {Richard S} and Liang Zhang and Ling Song",
year = "2000",
month = "4",
day = "15",
doi = "10.1006/abbi.2000.1728",
language = "English",
volume = "376",
pages = "365--370",
journal = "Archives of Biochemistry and Biophysics",
issn = "0003-9861",
publisher = "Academic Press Inc.",
number = "2",

}

TY - JOUR

T1 - Peroxynitrite modulates the activation of p38 and extracellular regulated kinases in PC12 cells

AU - Jope, Richard S

AU - Zhang, Liang

AU - Song, Ling

PY - 2000/4/15

Y1 - 2000/4/15

N2 - Although peroxynitrite appears to contribute to neuronal dysfunction in several neurodegenerative disorders, little is known about how peroxynitrite affects cellular signaling processes. This study investigated if peroxynitrite affects the mitogen-activated protein kinases, extracellular- regulated kinases 1 and 2 (ERK1/2) and p38. Exposure of PC12 cells to 500 μM peroxynitrite activated ERK1/2 and 938 within 5 min and this was followed by gradual decreases in activation over the next 25 min. Activation of ERK1/2 by peroxynitrite was mediated by activation of the epidermal growth factor (EGF) receptor in a calcium/calmodulin-dependent kinase II- and src family tyrosine kinase-dependent manner, as it was blocked by the selective EGF receptor inhibitor AG1478, by KN62, an inhibitor of calcium/calmodulin-dependent kinase II, and by PP1, a src family tyrosine kinase inhibitor. Activation of p38 by peroxynitrite was independent of the EGF receptor, required activation of calcium/calmodulin-dependent kinase II and src family tyrosine kinases, and was modulated by nerve growth factor (NGF) in a time-dependent manner. Pretreatment with NGF (2 h) attenuated, whereas cotreatment with NGF potentiated, peroxynitrite-induced activation of p38. Thus, peroxynitrite activates ERK1/2 and p38, activation of EGF receptors, calcium/calmodulin- dependent kinase II, and src family tyrosine kinases participate in these signaling responses to peroxynitrite, and peroxynitrite- and NGF-induced signaling activities converge on p38. (C) 2000 Academic Press.

AB - Although peroxynitrite appears to contribute to neuronal dysfunction in several neurodegenerative disorders, little is known about how peroxynitrite affects cellular signaling processes. This study investigated if peroxynitrite affects the mitogen-activated protein kinases, extracellular- regulated kinases 1 and 2 (ERK1/2) and p38. Exposure of PC12 cells to 500 μM peroxynitrite activated ERK1/2 and 938 within 5 min and this was followed by gradual decreases in activation over the next 25 min. Activation of ERK1/2 by peroxynitrite was mediated by activation of the epidermal growth factor (EGF) receptor in a calcium/calmodulin-dependent kinase II- and src family tyrosine kinase-dependent manner, as it was blocked by the selective EGF receptor inhibitor AG1478, by KN62, an inhibitor of calcium/calmodulin-dependent kinase II, and by PP1, a src family tyrosine kinase inhibitor. Activation of p38 by peroxynitrite was independent of the EGF receptor, required activation of calcium/calmodulin-dependent kinase II and src family tyrosine kinases, and was modulated by nerve growth factor (NGF) in a time-dependent manner. Pretreatment with NGF (2 h) attenuated, whereas cotreatment with NGF potentiated, peroxynitrite-induced activation of p38. Thus, peroxynitrite activates ERK1/2 and p38, activation of EGF receptors, calcium/calmodulin- dependent kinase II, and src family tyrosine kinases participate in these signaling responses to peroxynitrite, and peroxynitrite- and NGF-induced signaling activities converge on p38. (C) 2000 Academic Press.

KW - Alzheimer's disease

KW - ERK

KW - NGF

KW - Oxidative stress

KW - P38

KW - Peroxynitrite

UR - http://www.scopus.com/inward/record.url?scp=0034655604&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034655604&partnerID=8YFLogxK

U2 - 10.1006/abbi.2000.1728

DO - 10.1006/abbi.2000.1728

M3 - Article

C2 - 10775424

AN - SCOPUS:0034655604

VL - 376

SP - 365

EP - 370

JO - Archives of Biochemistry and Biophysics

JF - Archives of Biochemistry and Biophysics

SN - 0003-9861

IS - 2

ER -