Abstract
Hippocalcin is a neuronal calcium binding protein, but its physiological function in brain is unknown. We show here that hippocampal neurons from hippocalcin-deficient mice are more vulnerable to degeneration, particularly using thapsigargin, elevating intracellular calcium. Caspase-12 was activated in neurons lacking hippocalcin, while calpain was unchanged. Neuronal viability was accompanied by endoplasmic reticulum (ER) stress and a change in the relative induction of the ER chaperone, BiP/GRP78. Neuronal apoptosis inhibitor protein (NAIP), known to interact with hippocalcin, was not altered, but hippocampal neurons from gene-deleted mice were more sensitive to excitotoxicity caused by kainic acid. In addition, an age-dependent increase in neurodegeneration occurred in the gene-deleted mice, showing that hippocalcin contributes to neuronal viability during aging.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Aging / metabolism*
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Animals
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Calcium Signaling / drug effects
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Calcium Signaling / physiology
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Calcium-Binding Proteins / genetics
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Calcium-Binding Proteins / physiology*
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Caspase 12
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Caspases / metabolism*
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Cell Death / drug effects
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Cell Death / physiology
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Cell Survival / physiology
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Chimera
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Endoplasmic Reticulum / metabolism
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Endoplasmic Reticulum Chaperone BiP
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Female
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Heat-Shock Proteins / metabolism
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Hippocalcin
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Hippocampus / metabolism*
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Hippocampus / physiopathology
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Male
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Chaperones / metabolism
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Nerve Degeneration / chemically induced
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Nerve Degeneration / genetics
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Nerve Degeneration / metabolism*
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / physiology*
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Neuronal Apoptosis-Inhibitory Protein
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Oxidative Stress / physiology
Substances
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Calcium-Binding Proteins
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Endoplasmic Reticulum Chaperone BiP
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Enzyme Inhibitors
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Excitatory Amino Acid Agonists
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Heat-Shock Proteins
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Hpca protein, mouse
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Hspa5 protein, mouse
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Molecular Chaperones
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Naip1 protein, mouse
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Nerve Tissue Proteins
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Neuronal Apoptosis-Inhibitory Protein
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Hippocalcin
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Casp12 protein, mouse
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Caspase 12
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Caspases