+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Oxidative stress, nitric oxide, and the mechanisms of cell death in Lurcher Purkinje cells

Oxidative stress, nitric oxide, and the mechanisms of cell death in Lurcher Purkinje cells

Developmental Neurobiology 67(8): 1032-1046

Oxidative stress is postulated to play a role in cell death in many neurodegenerative diseases. As a model of neonatal neuronal cell death, we have examined the role of oxidative stress in Purkinje cell death in the heterozygous Lurcher mutant (+/Lc). Lurcher is a gain of function mutation in the delta2 glutamate receptor (GluRdelta2) that turns the receptor into a leaky membrane channel, resulting in chronic depolarization of +/Lc Purkinje cells starting around the first week of postnatal development. Virtually, all +/Lc Purkinje cells die by the end of the first postnatal month. To investigate the role of oxidative stress in +/Lc Purkinje cell death, we have examined nitric oxide synthase (NOS) activity and the expression of two markers for oxidative stress, nitrotyrosine and manganese super oxide dismutase (MnSOD), in wild type and +/Lc Purkinje cells at P10, P15, and P25. The results show that NOS activity and immunolabeling for nitrotyrosine and MnSOD are increased in +/Lc Purkinje cells. To determine whether peroxynitrite formation is a prerequisite for +/Lc Purkinje cell death, +/Lc mutants were crossed with an alpha-nNOS knockout mutant (nNOSalpha(-/-)) to reduce the production of NO. Analysis of the double mutants showed that blocking alpha-nNOS expression does not rescue +/Lc Purkinje cells. However, we present evidence for sustained NOS activity and nitrotyrosine formation in the GluRdelta2(+/Lc):nNOS(-/-) double mutant Purkinje cells, which suggests that the failure to rescue GluRdelta2(+/Lc):nNOS(-/-) Purkinje cells may be explained by the induction of alternative nNOS isoforms.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 016594103

Download citation: RISBibTeXText

PMID: 17565706

DOI: 10.1002/dneu.20391

Related references

Lurcher Purkinje cell death is accentuated in Lurcherreeler double mutants how is the GRID2LC channel killing Purkinje cells?. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 787 12, 2003

Mechanisms of compartmental purkinje cell death and survival in the lurcher mutant mouse. Cerebellum 10(3): 504-514, 2012

Nitric oxide protects the mitochondria of anterior pituitary cells and prevents cadmium-induced cell death by reducing oxidative stress. Free Radical Biology and Medicine 40(4): 679-688, 2006

Apoptotic cell death of myoblasts by oxidative stress and nitric oxide. Journal of the Neurological Sciences 150(SUPPL ): S176, 1997

Specific JNK inhibition by D-JNKI1 protects Purkinje cells from cell death in Lurcher mutant mouse. Cerebellum 7(4): 534-538, 2009

Antioxidant mechanisms of nitric oxide against iron-catalyzed oxidative stress in cells. Antioxidants and Redox Signaling 3(2): 189-202, 2001

N-acyl dopamines induce cell death in PC12 cell line via induction of nitric oxide generation and oxidative stress. Doklady. Biochemistry and Biophysics 467(1): 81-84, 2017

Induction of Inducible Nitric Oxide Synthase by Lipopolysaccharide and the Influences of Cell Volume Changes, Stress Hormones and Oxidative Stress on Nitric Oxide Efflux from the Perfused Liver of Air-Breathing Catfish, Heteropneustes fossilis. Plos One 11(3): E0150469, 2016

Interplay of cannabinoid 2 (CB2) receptors with nitric oxide synthases, oxidative and nitrative stress, and cell death during remote neurodegeneration. Journal of Molecular Medicine 90(4): 347-351, 2012

Endothelial nitric oxide synthase induced by doxorubicin in cardiomyocytes contributes to oxidative stress and apoptotic cell death. Circulation 104(17 Supplement): II 94, October 23, 2001

Dopamine modulation enhances manganese toxicity involving oxidative stress and inducible nitric oxide synthase a key mechanism for cell death. Society for Neuroscience Abstract Viewer & Itinerary Planner : Abstract No 946 5, 2003

Acceleration of oxidative stress-induced endothelial cell death by nitric oxide synthase dysfunction accompanied with decrease in tetrahydrobiopterin content. Life Sciences. 61(7): 739-747, 1997

Early generation of nitric oxide contributes to copper tolerance through reducing oxidative stress and cell death in hulless barley roots. Journal of Plant Research 129(5): 963-978, 2017

Nitric oxide and mitochondrial manganese superoxide dismutase regulate glucose-induced oxidative stress and programmed cell death in neurons. Neurology 56(8 Supplement 3): A394, April 24, 2001

Numerical matching between granule and Purkinje cells in lurcher chimeric mice: a hypothesis for the trophic rescue of granule cells from target-related cell death. Journal of Neuroscience 9(10): 3454-3462, 1989