Effect of nitration on protein tyrosine phosphatase and protein phosphatase activity in neuronal cell membranes of newborn piglets

López, Carlos Javier Más; Qayyum, Imran; Mishra, Om P.; Delivoria‐Papadopoulos, Maria

doi:10.1016/j.neulet.2005.04.089

Cited by 23 publications

(8 citation statements)

References 21 publications

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“…Oxidation of cysteine may inactivate tyrosine phosphatases [250,251]. Cytochrome nitration of cytochrome C severely impairs its redox activity and hence this is another target of peroxynitrite toxicity.…”

Section: Consequences Of Activated Inflamma-tory and Oandns Pathwaysmentioning

confidence: 99%

“…The weight of evidence now strongly indicates that peroxynitrite modulates phosphotyrosine signaling by modulating the activities of phosphotyrosine phosphatases and phosphotyrosine kinases. Thus, peroxynitrite even at miniscule doses irrevocably inhibits phosphotyrosine phosphatases [250,268]. Peroxynitrite impairs tyrosine phosphorylation which may cause deregulation of vital cellular activities [269,270].…”

Section: Consequences Of Activated Inflamma-tory and Oandns Pathwaysmentioning

confidence: 99%

See 1 more Smart Citation

Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Morris¹,

Maes

2014

114

139

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Myalgic Encephalomyelitis (ME) / Chronic Fatigue Syndrome (CFS) has been classified as a disease of the central nervous system by the WHO since 1969. Many patients carrying this diagnosis do demonstrate an almost bewildering array of biological abnormalities particularly the presence of oxidative and nitrosative stress (O&NS) and a chronically activated innate immune system. The proposal made herein is that once generated chronically activated O&NS and immune-inflammatory pathways conspire to generate a multitude of self-sustaining and self-amplifying pathological processes which are associated with the onset of ME/CFS. Sources of continuous activation of O&NS and immune-inflammatory pathways in ME/CFS are chronic, intermittent and opportunistic infections, bacterial translocation, autoimmune responses, mitochondrial dysfunctions, activation of the Toll-Like Receptor Radical Cycle, and decreased antioxidant levels. Consequences of chronically activated O&NS and immune-inflammatory pathways in ME/CFS are brain disorders, including neuroinflammation and brain hypometabolism / hypoperfusion, toxic effects of nitric oxide and peroxynitrite, lipid peroxidation and oxidative damage to DNA, secondary autoimmune responses directed against disrupted lipid membrane components and proteins, mitochondrial dysfunctions with a disruption of energy metabolism (e.g. compromised ATP production) and dysfunctional intracellular signaling pathways. The interplay between all of these factors leads to self-amplifying feed forward loops causing a chronic state of activated O&NS, immune-inflammatory and autoimmune pathways which may sustain the disease.

show abstract

Section: Consequences Of Activated Inflamma-tory and Oandns Pathwaysmentioning

confidence: 99%

Section: Consequences Of Activated Inflamma-tory and Oandns Pathwaysmentioning

confidence: 99%

Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Morris¹,

Maes

2014

114

139

View full text Add to dashboard Cite

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“…These proteins share a conserved cysteine residue within their active site, which is extremely sensitive to peroxynitrite-mediated oxidation and enzyme inactivation (19, 33–35). It has been proposed that, due to its structural similarities with phosphate anions, peroxynitrite might be attracted within the active site of the phosphatase, resulting in the oxidation of this critical cysteine-bound thiol and its subsequent inactivation (35).…”

Section: Redox Regulation Of Cell Signalling By Peroxynitritementioning

confidence: 99%

Role of peroxynitrite in the redox regulation of cell signal transduction pathways

Liaudet

Vassalli²,

Pacher³

2009

Front Biosci

190

131

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Peroxynitrite is a potent oxidant and nitrating species formed from the reaction between the free radicals nitric oxide and superoxide. An excessive formation of peroxynitrite represents an important mechanism contributing to cell death and dysfunction in multiple cardiovascular pathologies, such as myocardial infarction, heart failure and atherosclerosis. Whereas initial works focused on direct oxidative biomolecular damage as the main route of peroxynitrite toxicity, more recent evidence, mainly obtained in vitro, indicates that peroxynitrite also behaves as a potent modulator of various cell signal transduction pathways. Due to its ability to nitrate tyrosine residues, peroxynitrite affects cellular processes dependent on tyrosine phosphorylation. Peroxynitrite also exerts complex effects on the activity of various kinases and phosphatases, resulting in the up- or downregulation of signalling cascades, in a concentration- and cell-dependent manner. Such roles of peroxynitrite in the redox regulation of key signalling pathways for cardiovascular homeostasis, including protein kinase B and C, the MAP kinases, Nuclear Factor Kappa B, as well as signalling dependent on insulin and the sympatho-adrenergic system are presented in detail in this review.

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“…Altered protein phosphatase activity was implicated in the reduced PLB Serine16 phosphorylation observed in our previous study [7], but we did not directly examine whether peroxynitrite increases protein phosphatase activity in the myocardium or the role of specific protein phosphatases. Peroxynitrite has been shown to modulate the activity of certain types of protein phosphatases [11,12], but the effect on serine/threonine phosphatase activity has not been examined.…”

Section: Introductionmentioning

confidence: 99%

Peroxynitrite increases protein phosphatase activity and promotes the interaction of phospholamban with protein phosphatase 2a in the myocardium

2009

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High levels of peroxynitrite have been shown to decrease cardiomyocyte contraction through a reduction in phospholamban (PLB) phosphorylation. However, previous reports did not examine the direct effect of peroxynitrite on protein phosphatase activity in the myocardium or the role of specific phosphatases. Here we test the effect of the peroxynitrite donor SIN-1 on protein phosphatase activity in whole heart homogenates, as well as the interaction of PLB with protein phosphatase 1 (PP1) and 2a (PP2a). SIN-1 (200 μmol/L) induced a significant increase in protein phosphatase activity, which was alleviated with the specific PP1/PP2a inhibitor okadaic acid. Conversely, lower concentrations of SIN-1 and the nitric oxide donor spermine NONOate (300 μmol/L) were both without effect on phosphatase activity. We next examined the effect of SIN-1 on the interaction of PLB with PP1 and PP2a using co-immunoprecipitation, since okadaic acid inhibited the effects of SIN-1 in our current and previous studies. SIN-1 significantly increased the interaction of PLB with PP2a, but had no effect on the interaction between PLB and PP1. Urate, a peroxynitrite scavenger, inhibited the effects of SIN-1 on phosphatase activity and the interaction of PLB with PP2a, thus implicating peroxynitrite as the causal species. The results of this study provide further insight into the mechanism through which high levels of peroxynitrite serve to decrease PLB phosphorylation and myocardial contraction. Therefore, peroxynitrite signaling could play a key role in the contractile dysfunction manifested in heart failure where peroxynitrite production and protein phosphatase activity are increased and PLB phosphorylation is decreased.

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Effect of nitration on protein tyrosine phosphatase and protein phosphatase activity in neuronal cell membranes of newborn piglets

Cited by 23 publications

References 21 publications

Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Oxidative and Nitrosative Stress and Immune-inflammatory Pathways in Patients with Myalgic Encephalomyelitis (ME)/Chronic Fatigue Syndrome (CFS)

Role of peroxynitrite in the redox regulation of cell signal transduction pathways

Peroxynitrite increases protein phosphatase activity and promotes the interaction of phospholamban with protein phosphatase 2a in the myocardium

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