Over-expression of x-linked inhibitor of apoptosis protein modulates multiple aspects of neuronal Ca2+ signaling

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DOIResolve DOI: http://doi.org/10.1007/s11064-013-0989-0
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TypeArticle
Journal titleNeurochemical Research
ISSN0364-3190
Volume38
Issue4
Pages847856; # of pages: 10
Subjectbenzyloxycarbonylvalylalanylaspartyl fluoromethyl ketone; calcium ion; glutamic acid; n methyl dextro aspartic acid receptor; thapsigargin; voltage gated calcium channel; X linked inhibitor of apoptosis; animal cell; animal tissue; article; brain cortex; brain nerve cell; calcium cell level; calcium signaling; controlled study; embryo; female; male; mouse; neuromodulation; neuroprotection; nonhuman; priority journal; protein analysis; protein expression; protein function; receptor upregulation; transgenic mouse; transient transfection; wild type; Animals; Apoptosis; Calcium; Calcium Signaling; Glutamic Acid; Mice; Mice, Inbred C57BL; Mice, Transgenic; Neurons; Neuroprotective Agents; Oligopeptides; Thapsigargin; X-Linked Inhibitor of Apoptosis Protein; Mus; Mus musculus
AbstractX-linked inhibitor of apoptosis (XIAP) protects and preserves the function of neurons in both in vitro and in vivo models of excitotoxicity. Since calcium (Ca2+) overload is a pivotal event in excitotoxic neuronal cell death, we have determined whether XIAP over-expression influences Ca 2+-signaling in primary cultures of mouse cortical neurons. Using cortical neuron cultures derived from wild-type (Wt) mice transiently transfected with XIAP or from transgenic mice that over-express XIAP, we show that XIAP opposes the rise in intracellular Ca2+ concentration by a variety of triggers. Relative to control neurons, XIAP over-expression produced a slight, but significant, elevation of resting Ca2+ concentrations. By contrast, the rise in intracellular Ca2+ concentrations produced by N-methyl-d-aspartate receptor stimulation and voltage gated Ca2+ channel activation were markedly attenuated by XIAP over-expression. The release of Ca2+ from intracellular stores induced by the sarco/endoplasmic reticulum Ca2+ ATPase inhibitor thapsigargin was also inhibited in neurons transiently transfected with XIAP. The pan-caspase inhibitor zVAD did not, however, diminish the rise in intracellular Ca2+ concentrations elicited by l-glutamate suggesting that XIAP influences Ca2+ signaling in a caspase-independent manner. Taken together, these findings demonstrate that the ability of XIAP to block excessive rises in intracellular Ca2+ by a variety of triggers may contribute to the neuroprotective effects of this anti-apoptotic protein. © 2013 Springer Science+Business Media New York.
Publication date
LanguageEnglish
AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Nutrisciences and Health (INH-ISNS)
Peer reviewedYes
NPARC number21269749
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Record identifiera12b692b-d897-4e5e-ac6f-5c5b56fa5f3b
Record created2013-12-13
Record modified2016-05-09
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