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 journalArticle

35 Citations (Scopus)

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

Fingerprint

Calcineurin
Brain
Inositol
Ischemia
Phosphates
Apoptosis Regulatory Proteins
Neuroprotective Agents
In Vitro Techniques
Hypoxia
Immunoprecipitation
Caspase 3
Apoptosis
Biopsy

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

Cite this

Erin, N. ; Lehman, R. A.W. ; Boyer, P. J. ; Billingsley, M. L. / In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions. In: Neuroscience. 2003 ; Vol. 117, No. 3. pp. 557-565.
@article{53c1e37b5d21419ca4d57d4ecc5340bf,
title = "In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions",
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.",
author = "N. Erin and Lehman, {R. A.W.} and Boyer, {P. J.} and Billingsley, {M. L.}",
year = "2003",
month = "3",
day = "31",
doi = "10.1016/S0306-4522(02)00934-X",
language = "English (US)",
volume = "117",
pages = "557--565",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Limited",
number = "3",

}

In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions. / Erin, N.; Lehman, R. A.W.; Boyer, P. J.; Billingsley, M. L.

In: Neuroscience, Vol. 117, No. 3, 31.03.2003, p. 557-565.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vitro hypoxia and excitotoxicity in human brain induce calcineurin-Bcl-2 interactions

AU - Erin, N.

AU - Lehman, R. A.W.

AU - Boyer, P. J.

AU - Billingsley, M. L.

PY - 2003/3/31

Y1 - 2003/3/31

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=0344091560&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344091560&partnerID=8YFLogxK

U2 - 10.1016/S0306-4522(02)00934-X

DO - 10.1016/S0306-4522(02)00934-X

M3 - Article

C2 - 12617962

AN - SCOPUS:0344091560

VL - 117

SP - 557

EP - 565

JO - Neuroscience

JF - Neuroscience

SN - 0306-4522

IS - 3

ER -