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Induction of Nitric Oxide Synthase and Nitric Oxide‐Mediated Apoptosis in Neuronal PC12 Cells After Stimulation with Tumor Necrosis FActor‐α/Lipopolysaccharide
Author(s) -
Heneka Michael T.,
Löschmann PeterA.,
Gleichmann Marc,
Weller Michael,
Schulz Jörg B.,
Wüllner Ullrich,
Klockgether Thomas
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71010088.x
Subject(s) - nitric oxide , nitric oxide synthase , tumor necrosis factor alpha , apoptosis , lipopolysaccharide , programmed cell death , dna fragmentation , nerve growth factor , fragmentation (computing) , stimulation , microbiology and biotechnology , biology , necrosis , chemistry , endocrinology , medicine , biochemistry , receptor , ecology
Exposure of neuronal PC12 cells, differentiated by nerve growth factor, to tumor necrosis factor‐α (TNF‐α) and bacterial lipopolysaccharide (LPS) resulted in de novo synthesis of inducible nitric oxide synthase (iNOS) mRNA and protein with an increase up to 24 h. Brain NOS expression was unaffected. The induction of iNOS in differntiated PC12 cells was associated with cell death characterized by features of apoptosis, The NOS inhibitors N ‐monomethylarginine, aminoguanidine, and 2‐amino‐5,6‐dihydro‐6‐methyl‐4 H ‐1,3‐thiazine HCl prevented TNF‐α/LPS‐induced cell death and DNA fragmentation, suggesting that the TNF‐α/LPS‐induced cell death is mediated by iNOS‐derived NO. This hypothesis is supported by the finding that addition of l ‐arginine, which serves as a precursor and limiting factor of enzyme‐derived NO production, potentiated TNF‐α/LPS‐induced loss of viability.