Free 3-Nitrotyrosine Causes Striatal Neurodegeneration<i>In Vivo</i>

Mihm, Michael J.; Schanbacher, Brandon L; Wallace, Benjamin L.; Wallace, Lane J.; Uretsky, Norman J.; Bauer, John

doi:10.1523/jneurosci.21-11-j0003.2001

Cited by 67 publications

(48 citation statements)

References 24 publications

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“…Furthermore, MPTP and rotenone lead to complex I dysfunction with increased oxidative modification of proteins and (-synuclein aggregation (343). 6-hydroxydopamine, a neurotoxin, deletes GSH, a potent antioxidant, in brain striatum (305), causing striatal neurodegeneration in vivo (273). GAPDH, a critical enzyme in glycolysis and a protein with many other important functions (71), is also oxidized in sporadic PD (185).…”

Section: Redox Proteomics In Pdmentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

156

142

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Several studies demonstrated that oxidative damage is a characteristic feature of many neurodegenerative diseases. The accumulation of oxidatively modified proteins may disrupt cellular functions by affecting protein expression, protein turnover, cell signaling, and induction of apoptosis and necrosis, suggesting that protein oxidation could have both physiological and pathological significance. For nearly two decades, our laboratory focused particular attention on studying oxidative damage of proteins and how their chemical modifications induced by reactive oxygen species/reactive nitrogen species correlate with pathology, biochemical alterations, and clinical presentations of Alzheimer's disease. This comprehensive article outlines basic knowledge of oxidative modification of proteins and lipids, followed by the principles of redox proteomics analysis, which also involve recent advances of mass spectrometry technology, and its application to selected age-related neurodegenerative diseases. Redox proteomics results obtained in different diseases and animal models thereof may provide new insights into the main mechanisms involved in the pathogenesis and progression of oxidativestress-related neurodegenerative disorders. Redox proteomics can be considered a multifaceted approach that has the potential to provide insights into the molecular mechanisms of a disease, to find disease markers, as well as to identify potential targets for drug therapy. Considering the importance of a better understanding of the cause/effect of protein dysfunction in the pathogenesis and progression of neurodegenerative disorders, this article provides an overview of the intrinsic power of the redox proteomics approach together with the most significant results obtained by our laboratory and others during almost 10 years of research on neurodegenerative disorders since we initiated the field of redox proteomics. Antioxid. Redox Signal. 17, 1610-1655.

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Section: Redox Proteomics In Pdmentioning

confidence: 99%

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Butterfield

Perluigi

Reed

et al. 2012

Antioxidants & Redox Signaling

156

142

View full text Add to dashboard Cite

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“…The mechanism by which FP15 protects diabetic hearts from dysfunction may involve protection against vascular and myocardial tyrosine nitration, PARP activation, lipid peroxidation, and multiple other mechanisms, as all these mechanisms have previously been linked to diabetic cardiomyopathy as well as to peroxynitrite-induced cardiac injury. Additional mechanisms of peroxynitrite-mediated diabetic cardiac dysfunction may include inhibition of myofibrillar creatine kinase [85] and of succinyl-CoA:3-oxoacid CoAtransferase [27] or activation of metalloproteinases [45,86].…”

Section: Peroxynitrite Neutralization Improves Cardiac and Vascular Dmentioning

confidence: 99%

Role of Nitrosative Stress and Peroxynitrite in the Pathogenesis of Diabetic Complications. Emerging New Therapeutical Strategies

Pacher

Obrosova

Mabley

et al. 2005

CMC

306

243

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Macro-and microvascular disease are the most common causes of morbidity and mortality in patients with diabetes mellitus. Diabetic cardiovascular dysfunction represents a problem of great clinical importance underlying the development of various severe complications including retinopathy, nephropathy, neuropathy and increase the risk of stroke, hypertension and myocardial infarction. Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, are closely associated with increased oxidative and nitrosative stress, which can trigger the development of diabetic complications. Hyperglycemia stimulates the production of advanced glycosylated end products, activates protein kinase C, and enhances the polyol pathway leading to increased superoxide anion formation. Superoxide anion interacts with nitric oxide, forming the potent cytotoxin peroxynitrite, which attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, leading to cardiovascular dysfunction. The pathogenetic role of nitrosative stress and peroxynitrite, and downstream mechanisms including poly(ADP-ribose) polymerase (PARP) activation, is not limited to the diabetes-induced cardiovascular dysfunction, but also contributes to the development and progression of diabetic nephropathy, retinopathy and neuropathy. Accordingly, neutralization of peroxynitrite or pharmacological inhibition of PARP is a promising new approach in the therapy and prevention of diabetic complications. This review focuses on the role of nitrosative stress and downstream mechanisms including activation of PARP in diabetic complications and on novel emerging therapeutical strategies offered by neutralization of peroxynitrite and inhibition of PARP.

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“…For instance, striatal injection of free 3-nitrotyrosine at concentrations similar to 6-hydroxydopamine, which causes a well described degenerative pathology and a parkinsonian syndrome in rats, induced a selective loss of dopaminergic neurons (Mihm et al, 2001). Although these data suggest that dopaminergic neurons are particularly sensitive to 3-nitrotyrosine, the molecular basis of 3-nitrotyrosine deleterious effects is unknown.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of 3-Nitrotyrosine Induces Apoptotic Death in Dopaminergic Cells

Blanchard-Fillion

Prou

Polydoro

et al. 2006

Journal of Neuroscience

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Intrastriatal injection of 3-nitrotyrosine, which is a biomarker for nitrating oxidants, provokes dopaminergic neuronal death in rats by unknown mechanisms. Herein, we show that extracellular 3-nitrotyrosine is transported via the L-aromatic amino acid transporter in nondopaminergic NT2 cells, whereas in dopaminergic PC12 cells, it is transported by both the l-aromatic amino acid and the dopamine transporters. In both cell lines, 3-nitrotyrosine is a substrate for tyrosine tubulin ligase, resulting in its incorporation into the C terminus of ␣-tubulin. In NT2 cells, incorporation of 3-nitrotyrosine into ␣-tubulin induces a progressive, reversible reorganization of the microtubule architecture. In PC12 cells, 3-nitrotyrosine decreases intracellular dopamine levels and is metabolized by the concerted action of the aromatic amino acid decarboxylase and monoamine oxidase. Intracellular levels of 133 mol of 3-nitrotyrosine per mole of tyrosine did not alter NT2 viability but induced PC12 apoptosis. The cell death was reversed by caspases and aromatic amino acid decarboxylase and monoamine oxidase inhibitors. 3-Nitrotyrosine induced loss of tyrosine hydroxylase-positive primary rat neurons, which was also prevented by an aromatic amino acid decarboxylase inhibitor. These findings provide a novel mechanism by which products generated by reactive nitrogen species induce dopaminergic neuron death and thus may contribute to the selective neurodegeneration in Parkinson's disease.

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Free 3-Nitrotyrosine Causes Striatal NeurodegenerationIn Vivo

Cited by 67 publications

References 24 publications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Redox Proteomics in Selected Neurodegenerative Disorders: From Its Infancy to Future Applications

Role of Nitrosative Stress and Peroxynitrite in the Pathogenesis of Diabetic Complications. Emerging New Therapeutical Strategies

Metabolism of 3-Nitrotyrosine Induces Apoptotic Death in Dopaminergic Cells

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