In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions

N. Erin, R. A.W. Lehman, P. J. Boyer, M. L. Billingsley

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

Although pathogenesis of neuronal ischemia is incompletely understood, evidence indicates apoptotic neuronal death after ischemia. Bcl-2, an anti-apoptotic and neuroprotective protein, interacts with calcineurin in non-neuronal tissues. Activation of calcineurin, which is abundant in the brain, may play a role in apoptosis. Using co-immunoprecipitation experiments in biopsy-derived, fresh human cortical and hippocampal slices, we examined possible interactions between calcineurin and Bcl-2. Calcineuin-Bcl-2 interactions increased after exposure in vitro to excitotoxic agents and conditions of hypoxia/aglycia. This interaction may shuttle calcineurin to substrates such as the inositol-1,4,5-tris-phosphate receptor because under these experimental conditions interactions between calcineurin and inositol-1,4,5-tris-phosphate receptor also increased. A specific calcineurin inhibitor, FK-520, attenuated insult-induced increases in calcineurin-Bcl-2 interactions and augmented caspase-3 like activity. These data suggest that Bcl-2 modulates neuroprotective effects of calcineurin and that calcineurin inhibitors increase ischemic neuronal damage.

Original languageEnglish (US)
Pages (from-to)557-565
Number of pages9
JournalNeuroscience
Volume117
Issue number3
DOIs
StatePublished - Mar 31 2003

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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