Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2003-1-17
pubmed:abstractText
Nuclear factor-kappaB (NF-kappaB) is a transcription factor with a pivotal role in neuronal homeostasis. Indeed, NF-kappaB trans-activates several antiapoptotic genes in neurons and inhibition of NF-kappaB transcriptional activity triggers neuronal apoptosis. However, the exact mechanisms by which neurons undergo apoptosis in conditions of NF-kappaB inhibition are poorly understood. To further clarify how NF-kappaB operates in neurons, and to gather information on the molecular events occurring during NF-kappaB inhibition-dependent neuronal apoptosis, this study evaluated the effects of recently identified NF-kappaB inhibitors such as parthenolide, SN50, BAY 11-7082 and helenalin on primary cultures of rat cortical neurons. Data show that NF-kappaB was constitutively activated in neurons, and demonstrate for the first time that drug-dependent NF-kappaB inhibition induced rapid mitochondrial release of cytochrome c, caspase-9 and -3 activation, poly(ADP-ribose) polymerase-1 cleavage, membrane blebbing and nuclear fragmentation, without evidence of procaspase-8 and Bid processing. Interestingly, a burst of Akt activation occurred in neurons exposed to NF-kappaB inhibitors. These events were preceded by selective reduction of mRNAs of NF-kappaB-dependent, antiapoptotic Bcl-2 family members such as Bcl-x(L), Bcl-2 and, in particular, A1/Bfl-1. The present study reports a novel, detailed temporal analysis of the molecular events following impairment of NF-kappaB-driven transcription in neurons and demonstrates that inhibition of constitutive neuronal NF-kappaB activity triggers selective activation of the intrinsic apoptotic program.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/3-(4-methylphenylsulfonyl)-2-propene..., http://linkedlifedata.com/resource/pubmed/chemical/Adprt protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Anti-Inflammatory Agents..., http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents, http://linkedlifedata.com/resource/pubmed/chemical/Caspases, http://linkedlifedata.com/resource/pubmed/chemical/Cytochrome c Group, http://linkedlifedata.com/resource/pubmed/chemical/DNA, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/NF-kappa B, http://linkedlifedata.com/resource/pubmed/chemical/Nitriles, http://linkedlifedata.com/resource/pubmed/chemical/Organic Chemicals, http://linkedlifedata.com/resource/pubmed/chemical/Peptides, http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases, http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-bcl-2, http://linkedlifedata.com/resource/pubmed/chemical/Replication Protein C, http://linkedlifedata.com/resource/pubmed/chemical/SN50 peptide, http://linkedlifedata.com/resource/pubmed/chemical/Sesquiterpenes, http://linkedlifedata.com/resource/pubmed/chemical/Sulfones, http://linkedlifedata.com/resource/pubmed/chemical/helenalin, http://linkedlifedata.com/resource/pubmed/chemical/parthenolide
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
30
pubmed:volume
109
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
179-88
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12531527-Animals, pubmed-meshheading:12531527-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:12531527-Antineoplastic Agents, pubmed-meshheading:12531527-Apoptosis, pubmed-meshheading:12531527-Caspases, pubmed-meshheading:12531527-Cells, Cultured, pubmed-meshheading:12531527-Cerebral Cortex, pubmed-meshheading:12531527-Cytochrome c Group, pubmed-meshheading:12531527-DNA, pubmed-meshheading:12531527-DNA-Binding Proteins, pubmed-meshheading:12531527-Homeostasis, pubmed-meshheading:12531527-Mitochondria, pubmed-meshheading:12531527-NF-kappa B, pubmed-meshheading:12531527-Neurons, pubmed-meshheading:12531527-Nitriles, pubmed-meshheading:12531527-Organic Chemicals, pubmed-meshheading:12531527-Peptides, pubmed-meshheading:12531527-Poly(ADP-ribose) Polymerases, pubmed-meshheading:12531527-Protein Binding, pubmed-meshheading:12531527-Protein Precursors, pubmed-meshheading:12531527-Proteins, pubmed-meshheading:12531527-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:12531527-Rats, pubmed-meshheading:12531527-Replication Protein C, pubmed-meshheading:12531527-Sesquiterpenes, pubmed-meshheading:12531527-Sulfones, pubmed-meshheading:12531527-Transcription, Genetic
pubmed:year
2002
pubmed:articleTitle
Characterization of the molecular events following impairment of NF-kappaB-driven transcription in neurons.
pubmed:affiliation
Department of Cellular and Molecular Physiology, University of Massachusetts Medical School, Worcester, MA 01605, USA. albert_chiarugi@hotmail.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't