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Lysophosphatidic acid and apoptosis of nerve growth factor‐differentiated PC12 cells
Author(s) -
Holtsberg Frederick W.,
Steiner Marion R.,
BruceKeller Annadora J.,
Keller Jeffrey N.,
Mattson Mark P.,
Moyers John C.,
Steiner Sheldon M.
Publication year - 1998
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19980915)53:6<685::aid-jnr7>3.0.co;2-1
Subject(s) - lysophosphatidic acid , apoptosis , dna laddering , nitric oxide synthase , nitric oxide , oxidative stress , nerve growth factor , microbiology and biotechnology , cytochrome c , superoxide dismutase , biology , chemistry , biochemistry , programmed cell death , endocrinology , dna fragmentation , receptor
The lipid biomediator lysophosphatidic acid (LPA) elicits a unique response in hippocampal neurons, LPA induces neuronal apoptosis. This study explores the effects of LPA on cells with neuronal properties, nerve growth factor‐differentiated PC6 cells, a clone of PC12 cells. LPA induced apoptosis in these cells as assessed by chromatin condensation, terminal dUTP nick end‐labeling of DNA, protection against these nuclear alterations by a general caspase inhibitor and the lack of release of lactic dehydrogenase. LPA caused oxidative stress, namely a decreased reduction of MTT, 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide. This oxidative stress appears to be of functional significance, since cells were protected by pretreatment with the antioxidant propyl gallate and by stable transfection with cDNA encoding the antioxidant enzyme, manganese superoxide dismutase. Mitochondrial and nitric oxide participation in LPA‐induced apoptosis are suggested by the protection afforded by pretreatment with either cyclosporin A, an inhibitor of mitochondrial permeability transition, or nitric oxide synthase inhibitors. The nitric oxide synthase inhibitor findings are novel, since to our knowledge, LPA has not heretofore been associated with an increase in nitric oxide. In addition, as observed for many neurotoxic agents, insulin‐like growth factor I protected against LPA‐induced apoptosis of PC6 cells. J. Neurosci. Res. 53:685–696, 1998. © 1998 Wiley‐Liss, Inc.