Linked Life Data

11642660

Source:http://linkedlifedata.com/resource/pubmed/id/11642660

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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-10-19
pubmed:abstractText
1. Disruption of calcium homeostasis during neurodegenerative diseases is known to trigger apoptotic or necrotic death in neuronal cells. Recently, the authors reported that intracellular calcium restriction by NMDA receptor antagonists induces apoptosis in cortical cultures. To evaluate whether further restriction of intracellular free calcium can induce apoptosis or necrosis, we examined the neurotoxic characterization of BAPTA/AM, a permeable free calcium chelator, in mouse cortical cultures. 2. Exposure of mixed (glia and neuron) cortical cultures (DIV 13-16) to 3-10 microM BAPTA/AM (non-toxic concentration for glial cells) for 24-48 hr resulted in delayed and necrotic neuronal death. The necrotic findings included swelling and loss of mitochondria and endoplasmic reticulum (ER) with neuronal membrane rupture 24 hr after treatment with BAPTA/AM. Simultaneously, we observed a few TUNEL-positive cells in the neuronal subpopulation of the same cultures. 3. The neurotoxicity evoked by BAPTA/AM (10 microM) was significantly attenuated by the addition of 0.5 microM cycloheximide (a protein synthesis inhibitor), 10 microM actinomycin D (an RNA transcription inhibitor), a high extracellular potassium concentration (total 15 mM KCl), 100 microM t-ACPD (a metabotrophic agonist), 100 microM alpha-tocopherol (a free radical scavenger), 100 microM deferoxamine (a ferric ion chelator), 100 microM L-NAME (a nitric oxide synthase (NOS) inhibitor), 50 microM DNQX (a non-NMDA receptor blocker), and 3-30 microM esculetin (a lipoxygenase inhibitor). However, 0.3-3 mM ASA (a cyclooxygenase inhibitor), 100 ng/ml nerve growth factor (NGF), 10 microM MK-801 (a NMDA receptor antagonist), 20 microM zVAD-fmk (caspase inhibitor) and 50 U/ml catalase failed to inhibit the injury. 4. However, NGF and catalase blocked the neurotoxicity induced by BAPTA/AM in young neuronal cells (DIV 6). BAPTA/AM (10 microM) did not alter the expression of inducible nitric oxide synthase (iNOS) on glial cells. 5. These results suggest that the feature of neuronal death induced by BAPTA/AM exhibits predominantly delayed necrosis mediated by lipoxygenase-dependent free radicals.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0278-5846
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1641-59
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
BAPTA/AM, an intracellular calcium chelator, induces delayed necrosis by lipoxygenase-mediated free radicals in mouse cortical cultures.
pubmed:affiliation
Department of Veterinary Medicine and Institute of Life Science, Cheju National University, Korea. mbbwie@cheju.cheju.ac.kr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't