Abstract
Interleukin-1 beta (IL-1) and CREB have many CNS actions including sleep regulation and hippocampal-dependent learning. CREB acts in part via CREB-binding protein (CBP). We thus determined whether IL-1 could induce CBP gene expression. Initially, cultured hippocampal cells were treated with IL-1 and differential display reverse transcription was used to identify up- and down-regulated genes. We then sequenced rat CBP. Of the IL-1-upregulated genes, CBP and adenine nucleotide translocator-1 (ANT-1) were investigated in vivo. In these experiments, IL-1 was given to rats intraventricularly and sacrificed 2 h later; both CBP and ANT-1 transcripts were upregulated in the cerebral cortex and hypothalamus. We conclude that rat CBP shares many of the functional domains as human and murine CBP and that IL-1 upregulates genes previously associated with learning and sleep.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenine Nucleotide Translocator 1 / genetics
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Animals
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Brain / drug effects
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Brain / metabolism*
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Brain Chemistry / drug effects
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Brain Chemistry / genetics*
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CREB-Binding Protein
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Cells, Cultured
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Cerebral Cortex / drug effects
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Cerebral Cortex / metabolism
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Conserved Sequence / genetics
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / physiology*
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Humans
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Hypothalamus / drug effects
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Hypothalamus / metabolism
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Injections, Intraventricular
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Interleukin-1 / metabolism*
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Interleukin-1 / pharmacology
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Learning / physiology
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Male
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Mice
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Molecular Sequence Data
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Nuclear Proteins / genetics*
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Protein Structure, Tertiary / genetics
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RNA, Messenger / drug effects
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RNA, Messenger / metabolism*
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Rats
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Sequence Homology, Amino Acid
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Sequence Homology, Nucleic Acid
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Sleep / genetics
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Trans-Activators / genetics*
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Adenine Nucleotide Translocator 1
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Interleukin-1
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Nuclear Proteins
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RNA, Messenger
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Trans-Activators
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CREB-Binding Protein
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CREBBP protein, human
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Crebbp protein, mouse
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Crebbp protein, rat