Back to Search
Start Over
Superoxide dismutase activity in organotypic midbrain-striatum co-cultures is associated with resistance of dopaminergic neurons to excitotoxicity
- Source :
- Journal of Neurochemistry. 76:1336-1345
- Publication Year :
- 2001
- Publisher :
- Wiley, 2001.
-
Abstract
- We have previously demonstrated that dopaminergic neurons in midbrain-striatum slice co-cultures are more resistant to NMDA cytotoxicity than the same neuronal population in single midbrain slice cultures. Here, we show that dopaminergic neurons in midbrain-striatum co-cultures also exhibit resistance to the cytotoxicity of nitric oxide donors, 2,2'-(hydroxynitrosohydrazono)bis-ethanamine (NOC-18) and 3-morpholinosydnonimine (SIN-1). The cytotoxicity of NMDA (30 microM) in single cultures was significantly attenuated by the nitric oxide synthase (NOS) inhibitor N(omega)-nitro-L-arginine (100 microM), whereas the toxicity in co-cultures was not. The levels of tyrosine residue nitration of tyrosine hydroxylase, a hallmark of the occurence of peroxynitrite anion in dopaminergic neurons, were lower in co-cultures than those in single cultures. Single cultures and co-cultures did not show appreciable differences in the number or distribution of NOS-containing neurons as assessed by NADPH diaphorase histochemistry. On the other hand, midbrain slices cultured with striatal slices showed higher levels of superoxide dismutase (SOD) activity as well as increased protein levels of Cu,Zn-SOD, than midbrain slices cultured alone. These results suggested that the generation of NO is involved in NMDA cytotoxicity on dopaminergic neurons, and that increased activity of SOD in co-cultures renders dopaminergic neurons resistant to NMDA cytotoxicity by preventing the formation of peroxynitrite.
- Subjects :
- medicine.medical_specialty
Tyrosine hydroxylase
biology
Dopaminergic
Glutamate receptor
Excitotoxicity
Striatum
medicine.disease_cause
Biochemistry
Superoxide dismutase
Nitric oxide synthase
Cellular and Molecular Neuroscience
chemistry.chemical_compound
Endocrinology
nervous system
chemistry
Internal medicine
medicine
biology.protein
Peroxynitrite
Subjects
Details
- ISSN :
- 00223042
- Volume :
- 76
- Database :
- OpenAIRE
- Journal :
- Journal of Neurochemistry
- Accession number :
- edsair.doi...........d259278e1d0cbe591fbcc3de56f1cf0c