Hippocalcin protects against caspase-12-induced and age-dependent neuronal degeneration.
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.
Korhonen
Laura
L
Department of Neuroscience, Unit of Neurobiology, Uppsala University, Biomedical Centre, S-751 23 Uppsala, Sweden.
Hansson
Inga
I
Kukkonen
Jyrki P
JP
Brännvall
Karin
K
Kobayashi
Masaaki
M
Takamatsu
Ken
K
Lindholm
Dan
D
D000375:Aging / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000502:physiology*; D053454:Caspase 12; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D002678:Chimera; D004721:Endoplasmic Reticulum / Q000378:metabolism; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D005260:Female; D006360:Heat-Shock Proteins / Q000378:metabolism; D051597:Hippocalcin; D006624:Hippocampus / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018832:Molecular Chaperones / Q000378:metabolism; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D051616:Neuronal Apoptosis-Inhibitory Protein; D018384:Oxidative Stress / Q000502:physiology
D002135:Calcium-Binding Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D004791:Enzyme Inhibitors; D018690:Excitatory Amino Acid Agonists; D006360:Heat-Shock Proteins; C496692:Hpca protein, mouse; C000717248:Hspa5 protein, mouse; D018832:Molecular Chaperones; C496801:Naip1 protein, mouse; D009419:Nerve Tissue Proteins; D051616:Neuronal Apoptosis-Inhibitory Protein; D051597:Hippocalcin; C506440:Casp12 protein, mouse; D053454:Caspase 12; D020169:Caspases