Abstract |
Adenosine activates a signal transduction pathway (STP) in the heart and the brain, conferring protection against ischemia-reperfusion insult. Activation of protein kinase C (PKC), probably mainly PKC-epsilon, has been demonstrated to be part of the heart STP, but its role in the neuronal pathway is less clear. Here, we provide proof for the participation of PKC-epsilon in the neuronal adenosine-activated STP. Primary rat neuronal cultures were exposed to chemical ischemia by iodoacetate, followed by reperfusion. The cultured neurons were protected against this insult by activation of the adenosine mechanism, by N6-(R)-phenylisopropyladenosine [ R(-)-PIA], a specific A1 adenosine receptor agonist. Exposure of the cultures to bisindolylmaleimide I, a highly selective PKC inhibitor, abrogated the protection. The exposure of the cultures to R(-)-PIA was found to result in phosphorylation (activation) of PKC-epsilon. Furthermore, insertion into the cells of a specific peptide inhibitor of PKC-epsilon translocation (epsilonV1-2), also abrogated the protection conferred by R(-)-PIA. These results demonstrate that activation of PKC-epsilon is a vital step in the neuronal adenosine-activated STP.
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Authors | Noam Di-Capua, Oded Sperling, Esther Zoref-Shani |
Journal | Journal of neurochemistry
(J Neurochem)
Vol. 84
Issue 2
Pg. 409-12
(Jan 2003)
ISSN: 0022-3042 [Print] England |
PMID | 12559003
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Enzyme Activators
- Enzyme Inhibitors
- Iodoacetates
- Isoenzymes
- Prkce protein, rat
- Protein Kinase C
- Protein Kinase C-epsilon
- Adenosine
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Topics |
- Adenosine
(metabolism, pharmacology)
- Animals
- Cells, Cultured
- Enzyme Activation
(drug effects)
- Enzyme Activators
(pharmacology)
- Enzyme Inhibitors
(pharmacology)
- Iodoacetates
(pharmacology)
- Isoenzymes
(antagonists & inhibitors, metabolism)
- Neurons
(cytology, drug effects, metabolism)
- Phosphorylation
(drug effects)
- Protein Kinase C
(antagonists & inhibitors, metabolism)
- Protein Kinase C-epsilon
- Protein Transport
(drug effects)
- Rats
- Reperfusion Injury
(prevention & control)
- Signal Transduction
(drug effects, physiology)
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