Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-7-9
pubmed:abstractText
Caspase activation has been shown to be a critical step in several models of neuronal apoptosis such as staurosporine treatment of human neuroblastoma SH-SY5Y cells and potassium deprivation of rat cerebellar granule neurons. One common event is the appearance of caspase-mediated 120-kDa nonerythroid alpha-spectrin breakdown product (SBDP120). Second, inhibitors of the caspase family are effective blockers of such neuronal death. In this study, we report the appearance of caspase-mediated SBDP120 in excitotoxin-challenged fetal rat cerebrocortical neurons [N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid, and kainate] and rat cerebellar granule neurons (NMDA and kainate). A general caspase inhibitor, carbobenzoxy-Asp-CH2OC(O)-2,6-dichlorobenzene (Z-D-DCB), blocked the formation of SBDP120 under these conditions and attenuated the observed NMDA-induced lactate dehydrogenase (LDH) release in both cell types. Furthermore, hydrolytic activity toward a caspase-3-preferred synthetic peptide substrate, acetyl-DEVD-7-amido-4-methylcoumarin, was significantly elevated in NMDA-treated granule neurons. Lastly, oxygen-glucose deprivation (OGD)-challenged cerebrocortical cultures also showed the appearance of SBDP120. Again, Z-D-DCB blocked the SBDP120 formation as well as attenuated the LDH release from the OGD-challenged neurons. Taken together, the presence of caspase-specific SBDP120 and the neuroprotective effects of Z-D-DCB strongly suggest that caspase activation contributes at least in part to excitotoxin- and OGD-induced neuronal death.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/CASP3 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Casp3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Cysteine Endopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Agonists, http://linkedlifedata.com/resource/pubmed/chemical/Glucose, http://linkedlifedata.com/resource/pubmed/chemical/Kainic Acid, http://linkedlifedata.com/resource/pubmed/chemical/N-Methylaspartate, http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins, http://linkedlifedata.com/resource/pubmed/chemical/Oligopeptides, http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments, http://linkedlifedata.com/resource/pubmed/chemical/Protease Inhibitors, http://linkedlifedata.com/resource/pubmed/chemical/Spectrin, http://linkedlifedata.com/resource/pubmed/chemical/benzyloxycarbonyl-Glu-Val-Asp-CH2OC(...
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
186-95
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9648865-Animals, pubmed-meshheading:9648865-Caspase 3, pubmed-meshheading:9648865-Caspases, pubmed-meshheading:9648865-Cell Death, pubmed-meshheading:9648865-Cell Hypoxia, pubmed-meshheading:9648865-Cells, Cultured, pubmed-meshheading:9648865-Cerebellum, pubmed-meshheading:9648865-Cerebral Cortex, pubmed-meshheading:9648865-Cysteine Endopeptidases, pubmed-meshheading:9648865-Enzyme Precursors, pubmed-meshheading:9648865-Excitatory Amino Acid Agonists, pubmed-meshheading:9648865-Fetus, pubmed-meshheading:9648865-Glucose, pubmed-meshheading:9648865-Hypoglycemia, pubmed-meshheading:9648865-Kainic Acid, pubmed-meshheading:9648865-N-Methylaspartate, pubmed-meshheading:9648865-Neurons, pubmed-meshheading:9648865-Neurotoxins, pubmed-meshheading:9648865-Oligopeptides, pubmed-meshheading:9648865-Peptide Fragments, pubmed-meshheading:9648865-Protease Inhibitors, pubmed-meshheading:9648865-Rats, pubmed-meshheading:9648865-Rats, Sprague-Dawley, pubmed-meshheading:9648865-Spectrin
pubmed:year
1998
pubmed:articleTitle
Evidence for activation of caspase-3-like protease in excitotoxin- and hypoxia/hypoglycemia-injured neurons.
pubmed:affiliation
Department of Neuroscience Therapeutics, Parke-Davis Pharmaceutical Research, Warner-Lambert Company, Ann Arbor, Michigan 48105, USA.
pubmed:publicationType
Journal Article