Preconditioning mediated by sublethal oxygen-glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (εPKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or εPKC activation. Inhibition of either εPKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after εPKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

Original languageEnglish
Pages (from-to)1329-1340
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume28
Issue number7
DOIs
StatePublished - Jul 1 2008

Fingerprint

STAT3 Transcription Factor
Cyclooxygenase 2
Phosphorylation
Oxygen
Glucose
Protein Kinase C
Transducers
Serine
Protein Kinase C-epsilon
MAP Kinase Signaling System
Mitogen-Activated Protein Kinase 1
Astrocytes
Protein Isoforms
Ischemia
Cell Culture Techniques
Neurons

Keywords

  • Cerebral ischemia
  • Extracellular signal-regulated kinase (ERK1/2)
  • Ischemic tolerance
  • Neuroprotection
  • Phosphorylation
  • Protein kinase C

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)
  • Endocrinology, Diabetes and Metabolism

Cite this

@article{40645c09ee7d4ef38bd6b1cbd71688ed,
title = "Preconditioning mediated by sublethal oxygen-glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation",
abstract = "The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (εPKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or εPKC activation. Inhibition of either εPKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after εPKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.",
keywords = "Cerebral ischemia, Extracellular signal-regulated kinase (ERK1/2), Ischemic tolerance, Neuroprotection, Phosphorylation, Protein kinase C",
author = "Kim, {Eun J.} and Ami Raval and Miguel Perez-Pinzon",
year = "2008",
month = "7",
day = "1",
doi = "10.1038/jcbfm.2008.26",
language = "English",
volume = "28",
pages = "1329--1340",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Preconditioning mediated by sublethal oxygen-glucose deprivation-induced cyclooxygenase-2 expression via the signal transducers and activators of transcription 3 phosphorylation

AU - Kim, Eun J.

AU - Raval, Ami

AU - Perez-Pinzon, Miguel

PY - 2008/7/1

Y1 - 2008/7/1

N2 - The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (εPKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or εPKC activation. Inhibition of either εPKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after εPKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

AB - The signal transducers and activators of transcription (STATs) were found to be essential for cardioprotection. However, their role in preconditioning (PC) neuroprotection remains undefined. Previously, our studies showed that PC mediated a signaling cascade that involves activation of epsilon protein kinase C (εPKC), extracellular signal-regulated kinase (ERK1/2), and cyclooxygenase-2 (COX-2) pathways. However, the intermediate pathway by which ERK1/2 activates COX-2 was not defined. In this study, we investigated whether the PC-induced signaling pathway requires phosphorylation of STAT isoforms for COX-2 expression. To mimic PC or lethal ischemia, mixed cortical neuron/astrocyte cell cultures were subjected to 1 and/or 4 h of oxygen-glucose deprivation (OGD), respectively. The results indicated serine phosphorylation of STAT3 after PC or εPKC activation. Inhibition of either εPKC or ERK1/2 activation abolished PC-induced serine phosphorylation of STAT3. Additionally, inhibition of STAT3 prevented PC-induced COX-2 expression and neuroprotection against OGD. Therefore, our findings suggest that PC signaling cascade involves STAT3 activation after εPKC and ERK1/2 activation. Finally, we show that STAT3 activation mediates COX-2 expression and ischemic tolerance.

KW - Cerebral ischemia

KW - Extracellular signal-regulated kinase (ERK1/2)

KW - Ischemic tolerance

KW - Neuroprotection

KW - Phosphorylation

KW - Protein kinase C

UR - http://www.scopus.com/inward/record.url?scp=46049100787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=46049100787&partnerID=8YFLogxK

U2 - 10.1038/jcbfm.2008.26

DO - 10.1038/jcbfm.2008.26

M3 - Article

C2 - 18398416

AN - SCOPUS:46049100787

VL - 28

SP - 1329

EP - 1340

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 7

ER -