Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide.

HENEKA, Michael; Löschmann, Peter-A.; Gleichmann, Marc; Weller, Michael; Schulz, Jörg B.; Wüllner, Ullrich; Klockgether, Thomas

doi:10.1046/j.1471-4159.1998.71010088.x

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Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide.

HENEKA, Michael; Löschmann, Peter-A.; Gleichmann, Marc et al.

1998 • In Journal of Neurochemistry, 71 (1), p. 88 - 94

Peer Reviewed verified by ORBi

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https://hdl.handle.net/10993/60982

DOI
10.1046/j.1471-4159.1998.71010088.x

PubMed
9648854

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Keywords :

2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine; Deoxyuracil Nucleotides; Enzyme Inhibitors; Guanidines; Lipopolysaccharides; RNA, Messenger; Thiazines; Tumor Necrosis Factor-alpha; omega-N-Methylarginine; Nitric Oxide; Biotin; Arginine; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nos2 protein, rat; pimagedine; Animals; Apoptosis/drug effects; Apoptosis/physiology; Arginine/pharmacology; Cell Differentiation/physiology; DNA Fragmentation; Enzyme Inhibitors/pharmacology; Gene Expression Regulation, Enzymologic/physiology; Guanidines/pharmacology; Lipopolysaccharides/pharmacology; Neurons/cytology; Neurons/drug effects; Neurons/enzymology; Nitric Oxide/metabolism; Nitric Oxide Synthase/antagonists & inhibitors; Nitric Oxide Synthase/genetics; Nitric Oxide Synthase/metabolism; PC12 Cells; RNA, Messenger/analysis; Rats; Staining and Labeling; Thiazines/pharmacology; Transcription, Genetic/physiology; Tumor Necrosis Factor-alpha/pharmacology; omega-N-Methylarginine/pharmacology; Apoptosis; Differentiated PC12 cells; Inducible nitric oxide synthase; N- Monomethylarginine; Biochemistry; Cellular and Molecular Neuroscience; N-monomethylarginine

Abstract :

[en] Exposure of neuronal PC12 cells, differentiated by nerve growth factor, to tumor necrosis factor-alpha (TNF-alpha) 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 differentiated 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-4H-1,3-thiazine.HCl prevented TNF-alpha/LPS-induced cell death and DNA fragmentation, suggesting that the TNF-alpha/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-alpha/LPS-induced loss of viability.

Disciplines :

Neurology

Author, co-author :

HENEKA, Michael ; Department of Neurology, University of Tübingen, Germany

Löschmann, Peter-A.; Department of Neurology, University of Tübingen, Tübingen, Germany

Gleichmann, Marc; Department of Neurology, University of Tübingen, Tübingen, Germany

Weller, Michael; Department of Neurology, University of Tübingen, Tübingen, Germany

Schulz, Jörg B.; Department of Neurology, University of Tübingen, Tübingen, Germany

Wüllner, Ullrich; Department of Neurology, University of Tübingen, Tübingen, Germany

Klockgether, Thomas; Department of Neurology, University of Tübingen, Tübingen, Germany

External co-authors :

yes

Language :

English

Title :

Induction of nitric oxide synthase and nitric oxide-mediated apoptosis in neuronal PC12 cells after stimulation with tumor necrosis factor-alpha/lipopolysaccharide.

Publication date :

July 1998

Journal title :

Journal of Neurochemistry

ISSN :

0022-3042

eISSN :

1471-4159

Publisher :

Blackwell Publishing Ltd, England

Volume :

Issue :

Pages :

88 - 94

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1046%2Fj.1471-4159.1998.71010088.x

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since 07 May 2024

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