Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation

Ami Raval, Kunjan R Dave, Ricardo Prado, Laurence M. Katz, Raul Busto, Thomas Sick, Myron Ginsberg, Daria Mochly-Rosen, Miguel Perez-Pinzon

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. δPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted δPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced δPKC translocation and increased its cleavage at 3 h of reperfusion. Since δPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either δPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of δPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote δPKC translocation/cleavage.

Original languageEnglish
Pages (from-to)730-741
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume25
Issue number6
DOIs
StatePublished - Jun 1 2005

Fingerprint

Protein Kinase C-delta
Heart Arrest
Protein Kinase C
Signal Transduction
Caspase 3
Oxygen
Glucose
Reperfusion
Cytochromes c
Reperfusion Injury
Brain Ischemia
Cytosol
Isoenzymes
Hippocampus
Apoptosis

Keywords

  • Caspase 3
  • Cytochrome c
  • Global ischemia
  • Hippocampus
  • Neurodegeneration
  • Organotypic slice cultures

ASJC Scopus subject areas

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

Cite this

Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation. / Raval, Ami; Dave, Kunjan R; Prado, Ricardo; Katz, Laurence M.; Busto, Raul; Sick, Thomas; Ginsberg, Myron; Mochly-Rosen, Daria; Perez-Pinzon, Miguel.

In: Journal of Cerebral Blood Flow and Metabolism, Vol. 25, No. 6, 01.06.2005, p. 730-741.

Research output: Contribution to journalArticle

@article{cb8ebec7e3374aaf8bfa6e36106d21eb,
title = "Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation",
abstract = "Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. δPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted δPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced δPKC translocation and increased its cleavage at 3 h of reperfusion. Since δPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either δPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of δPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote δPKC translocation/cleavage.",
keywords = "Caspase 3, Cytochrome c, Global ischemia, Hippocampus, Neurodegeneration, Organotypic slice cultures",
author = "Ami Raval and Dave, {Kunjan R} and Ricardo Prado and Katz, {Laurence M.} and Raul Busto and Thomas Sick and Myron Ginsberg and Daria Mochly-Rosen and Miguel Perez-Pinzon",
year = "2005",
month = "6",
day = "1",
doi = "10.1038/sj.jcbfm.9600071",
language = "English",
volume = "25",
pages = "730--741",
journal = "Journal of Cerebral Blood Flow and Metabolism",
issn = "0271-678X",
publisher = "Nature Publishing Group",
number = "6",

}

TY - JOUR

T1 - Protein kinase C delta cleavage initiates an aberrant signal transduction pathway after cardiac arrest and oxygen glucose deprivation

AU - Raval, Ami

AU - Dave, Kunjan R

AU - Prado, Ricardo

AU - Katz, Laurence M.

AU - Busto, Raul

AU - Sick, Thomas

AU - Ginsberg, Myron

AU - Mochly-Rosen, Daria

AU - Perez-Pinzon, Miguel

PY - 2005/6/1

Y1 - 2005/6/1

N2 - Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. δPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted δPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced δPKC translocation and increased its cleavage at 3 h of reperfusion. Since δPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either δPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of δPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote δPKC translocation/cleavage.

AB - Protein kinase C (PKC) isozymes have been known to mediate a variety of complex and diverse cellular functions. δPKC has been implicated in mediating apoptosis. Using two models of cerebral ischemia, cardiac arrest in rats and oxygen glucose deprivation (OGD) in organotypic hippocampal slices, we tested whether an ischemic insult promoted δPKC cleavage during the reperfusion and whether the upstream pathway involved release of cytochrome c and caspase 3 cleavage. We showed that cardiac arrest/OGD significantly enhanced δPKC translocation and increased its cleavage at 3 h of reperfusion. Since δPKC is one of the substrates for caspase 3, we next determined caspase 3 activation after cardiac arrest and OGD. The maximum decrease in levels of procaspase 3 was observed at 3 h of reperfusion after cardiac arrest and OGD. We also determined cytochrome c release, since it is upstream of caspase 3 activation. Cytochrome c in cytosol increased at 1 h of reperfusion after cardiac arrest/OGD. Inhibition of either δPKC/caspase 3 during OGD and early reperfusion resulted in neuroprotection in CA1 region of hippocampus. Our results support the deleterious role of δPKC in reperfusion injury. We propose that early cytochrome c release and caspase 3 activation promote δPKC translocation/cleavage.

KW - Caspase 3

KW - Cytochrome c

KW - Global ischemia

KW - Hippocampus

KW - Neurodegeneration

KW - Organotypic slice cultures

UR - http://www.scopus.com/inward/record.url?scp=18944383054&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18944383054&partnerID=8YFLogxK

U2 - 10.1038/sj.jcbfm.9600071

DO - 10.1038/sj.jcbfm.9600071

M3 - Article

C2 - 15716854

AN - SCOPUS:18944383054

VL - 25

SP - 730

EP - 741

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

SN - 0271-678X

IS - 6

ER -