Abstract
Adenosine is considered an endogenous neuroprotective metabolite that through activation of the A(1) receptor results in reduction of neuronal damage following cerebral ischemia. Protein kinase B, also known as Akt/PKB, is part of an endogenous pathway that exerts effective neuroprotection from both necrotic and apoptotic cell death. Using a rat model of unilateral common carotid artery occlusion coupled with hypoxia, and using in vitro rat hippocampal slices, we examined the ability of adenosine to directly activate Akt/PKB. Western blot analysis revealed that levels of phosphorylated Akt/PKB were elevated in vivo under ischemic conditions in an adenosine A(1)-dependent manner and elevated in hippocampal slices treated with an adenosine A(1) agonist. We conclude from these studies that the activation of an adenosine A(1) receptor-mediated signal transduction pathway, either by endogenous adenosine (in vivo) or by an adenosine A(1) agonist (in vitro), results in the activation of the neurotrophic kinase Akt/PKB.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenosine / agonists
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Adenosine / analogs & derivatives*
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Adenosine / metabolism*
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Adenosine / pharmacology
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Animals
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Cell Death / drug effects
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Cell Death / physiology
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Cerebrovascular Circulation / drug effects
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Cerebrovascular Circulation / physiology
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Hippocampus / drug effects
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Hippocampus / enzymology*
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Hippocampus / physiopathology
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Hypoxia-Ischemia, Brain / drug therapy
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Hypoxia-Ischemia, Brain / enzymology*
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Hypoxia-Ischemia, Brain / physiopathology
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Immunohistochemistry
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Male
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Nerve Degeneration / drug therapy
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Nerve Degeneration / enzymology
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Neurons / drug effects
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Neurons / enzymology*
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Neurons / pathology
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Organ Culture Techniques
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Phosphorylation
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / drug effects
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Proto-Oncogene Proteins / metabolism*
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Proto-Oncogene Proteins c-akt
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Rats
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Rats, Sprague-Dawley
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Receptors, Purinergic P1 / metabolism*
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Subcellular Fractions / drug effects
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Subcellular Fractions / metabolism
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
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Theophylline / analogs & derivatives*
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Theophylline / pharmacology
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Up-Regulation / drug effects
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Up-Regulation / physiology
Substances
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Proto-Oncogene Proteins
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Purinergic P1 Receptor Agonists
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Purinergic P1 Receptor Antagonists
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Receptors, Purinergic P1
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8-cyclopentyl-1,3-dimethylxanthine
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N(6)-cyclohexyladenosine
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Theophylline
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Adenosine