Abstract
Defects in intracellular calcium homeostasis may cause aberrant neuronal activation and subsequent neuronal death. Because inositol trisphosphate (IP(3)) regulates the release of calcium from the endoplasmic reticulum and the IP(3) kinase A isoform (IP(3)K-A) reduces intracellular IP(3), regulation of IP(3)K could be involved in neuronal activation and/or neuronal death. In this study, we found that kainic acid (KA) treatment in vitro and in vivo reduced the level of IP(3)K-A mRNA. Since KA treatment induces aberrant neuronal activation and neuronal death, we tested whether the reduction of IP(3)K-A mRNA was required for KA-induced neuronal death. Overexpression of adenovirus-derived IP(3)K-A failed to rescue neurons from KA-induced death. Because neuronal activation by KCl in vitro is sufficient to reduce IP(3)K-A expression, we conclude that the KA-derived reduction of IP(3)K-A expression is due to the aberrant neuronal activation, and the reduction in the IP3K-A mRNA level is not required for the toxic effect of KA.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Blotting, Northern / methods
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Blotting, Western / methods
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Brain / cytology
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Brain / drug effects*
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Brain / enzymology
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Cells, Cultured
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Embryo, Mammalian
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Enzyme Activation / drug effects
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Excitatory Amino Acid Agonists / pharmacology*
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Gene Expression Regulation, Enzymologic / drug effects*
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Glial Fibrillary Acidic Protein / genetics
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Glial Fibrillary Acidic Protein / metabolism
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HSP70 Heat-Shock Proteins / genetics
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HSP70 Heat-Shock Proteins / metabolism
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HSP90 Heat-Shock Proteins
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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Kainic Acid / pharmacology*
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Male
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Neurons / drug effects
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Neurons / enzymology
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Phosphotransferases (Alcohol Group Acceptor) / genetics
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Phosphotransferases (Alcohol Group Acceptor) / metabolism*
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-fos / metabolism
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RNA, Messenger / biosynthesis
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Rats
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Rats, Sprague-Dawley
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Time Factors
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Transfection / methods
Substances
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Excitatory Amino Acid Agonists
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Glial Fibrillary Acidic Protein
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HSP70 Heat-Shock Proteins
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HSP90 Heat-Shock Proteins
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Proto-Oncogene Proteins c-fos
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RNA, Messenger
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TRAP1 protein, rat
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Phosphotransferases (Alcohol Group Acceptor)
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Inositol 1,4,5-trisphosphate 3-kinase
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Kainic Acid