Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1996-10-24
pubmed:abstractText
Chromogranin A is an ubiquitous 48,000 mol. wt secretory protein stored and released from many neuroendocrine cells and neurons. In human brain, chromogranin A is a common feature of regions that are known to be affected by various neurodegenerative pathologies such as Alzheimer's, Parkinson's and Pick's diseases. Brain degenerative areas are generally infiltrated by activated microglial cells, the resident macrophage cell population within the central nervous system. Here, we report that both recombinant human chromogranin A and chromogranin A purified from bovine chromaffin granules trigger drastic morphological changes in rat microglial cells maintained in culture. Microglial cells exposed to chromogranin A adopted a flattened amoeboid shape and, this change was associated with an accumulation of actin in the subplasmalemmal region, as observed by immunocytochemistry and confocal laser microscopy. In single microglial cells loaded with indo-1, chromogranin A elicited a rapid and transient increase in [Ca2+]i which preceded the reorganization of actin cytoskeleton. The activity of nitric oxide synthase was estimated by measuring the accumulation of nitrite in the culture medium. Both recombinant human chromogranin A and bovine chromogranin A triggered an important accumulation of nitrite comparable to that induced by lipopolysaccharide, a well-known activator of microglia. The effect of chromogranin A was dose dependent, inhibited by N omega-nitro-L-arginine methyl ester, a competitive inhibitor of nitric oxide synthase, and by cycloheximide, an inhibitor of protein synthesis. These findings suggest that chromogranin A induces an activated phenotype of microglia, and thus may have a role in the pathogenesis of neuronal degeneration in the brain.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0306-4522
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
377-89
pubmed:dateRevised
2007-4-17
pubmed:meshHeading
pubmed-meshheading:8737408-Actins, pubmed-meshheading:8737408-Animals, pubmed-meshheading:8737408-Brain, pubmed-meshheading:8737408-Brain Chemistry, pubmed-meshheading:8737408-Calcium, pubmed-meshheading:8737408-Cattle, pubmed-meshheading:8737408-Chromogranin A, pubmed-meshheading:8737408-Chromogranins, pubmed-meshheading:8737408-Fluorescent Antibody Technique, Direct, pubmed-meshheading:8737408-Humans, pubmed-meshheading:8737408-Image Processing, Computer-Assisted, pubmed-meshheading:8737408-Lipopolysaccharides, pubmed-meshheading:8737408-Microglia, pubmed-meshheading:8737408-Microscopy, Confocal, pubmed-meshheading:8737408-Nitric Oxide, pubmed-meshheading:8737408-Phenotype, pubmed-meshheading:8737408-Precipitin Tests, pubmed-meshheading:8737408-Rats, pubmed-meshheading:8737408-Rats, Wistar, pubmed-meshheading:8737408-Recombinant Proteins
pubmed:year
1996
pubmed:articleTitle
Chromogranin A triggers a phenotypic transformation and the generation of nitric oxide in brain microglial cells.
pubmed:affiliation
Unité INSERM U-338 Biologie de la Communication Cellulaire, Strasbourg, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't