Lysophosphatidic acid induction of neuronal apoptosis and necrosis

Marion R. Steiner, Frederick W. Holtsberg, Jeffrey N. Keller, Mark P. Mattson, Sheldon M. Steiner

Research output: Contribution to journalArticle

Abstract

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 μM LPA resulted in necrosis, as determined morphologically and by release of lactate dehydrogenase. Lower concentrations of LPA, 0.1, and 1 μM, 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 μM 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.

Original languageEnglish (US)
Pages (from-to)132-141
Number of pages10
JournalAnnals of the New York Academy of Sciences
Volume905
StatePublished - 2000
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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  • Cite this

    Steiner, M. R., Holtsberg, F. W., Keller, J. N., Mattson, M. P., & Steiner, S. M. (2000). Lysophosphatidic acid induction of neuronal apoptosis and necrosis. Annals of the New York Academy of Sciences, 905, 132-141.