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PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-6-5
pubmed:abstractText
Lysophosphatidic acid (LPA) elicits a unique response in primary hippocampal neurons and sympathetic neuron-like cells, PC12 cells differentiated with nerve growth factor; LPA is cytotoxic. Treatment of rat hippocampal neurons with 50 microM LPA resulted in necrosis, as determined morphologically and by release of lactate dehydrogenase. Lower concentrations of LPA, 0.1, and 1 microM, induced neuronal apoptosis, as assessed by chromatin condensation, annexin V binding, TUNEL staining, and the caspase sensitivity of these events. In addition, 10 and 25 microM LPA induced apoptosis of PC12 cells. In order to define intracellular events associated with this neuronal apoptosis, protective agents were identified. Neurons and PC12 cells were protected against LPA-induced apoptosis by pretreatment with the antioxidant, propyl gallate, or with nitric oxide synthase inhibitors. PC12 cells were protected by insulin and insulin-like growth-factor-1 treatment. There is also evidence for mitochondrial participation in LPA-mediated apoptosis, including cyclosporin A-mediated protection. Thus, LPA-induced neuronal apoptosis is associated with mitochondrial alterations, the generation of reactive oxygen species and nitric oxide, and protection by pretreatment with a serum constituent, insulin-like growth factor 1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0077-8923
pubmed:author
pubmed:issnType
Print
pubmed:volume
905
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
132-41
pubmed:dateRevised
2003-11-14
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Lysophosphatidic acid induction of neuronal apoptosis and necrosis.
pubmed:affiliation
Department of Microbiology and Immunology, University of Kentucky, Lexington 40536, USA. mrstei01@pop.uky.edy
pubmed:publicationType
Journal Article