Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means of<i>S</i>-nitrosylation

Park, Hee Sae; Huh, Sung Ho; Kim, Mi Sung; Lee, Soo Hwan; Choi, Eui Ju

doi:10.1073/pnas.97.26.14382

Cited by 229 publications

(184 citation statements)

References 50 publications

(51 reference statements)

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“…However, the inhibition of ERK1/2 activation has been shown to protect a mouse neuronal cell line and rat primary cortical neurons form oxidative stress-induced neurotoxicity [1] demonstrating a possible involvement in cell death. The JNK signaling cascade has been reported to be activated by a wide range of different oxidants/reductants including hydrogen peroxide [135,218], lipid peroxidation products [6,191], different types of radiation [63], modulators of intracellular glutathione status [145], peroxynitrite [71], glutamate [180], dithiothreitol, and nitric oxide [152]. Although the links between redox status and MAPK signaling have been known for some time, data demonstrating the molecular basis of such links and identifying the sensors in this redox response are few.…”

Section: Mapk Signaling Under Oxidative Stressmentioning

confidence: 99%

“…Thus, it has been proposed that this cysteine reside may represent an important molecular redox trigger, whereby cells can respond to the ambient redox status. Indeed, through Ras activation, NO • -related species can modulate the activity of all three MAPKs [114,115,152]. For example, activation of ERK1/2, as discussed earlier, may lead to the phosphorylation/inactivation of the pro-apoptotic protein Bad, the expression of anti-apoptotic proteins such as Bcl-2 and the suppression of pro-apoptotic proteins such as Bax (see above) (Fig.…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

“…6). In contrast, however, NO • can directly suppress JNK activation via S-nitrosation of a redox-sensitive residue that is not present on ERK or p38 [152,190], thereby supporting pro-survival mechanisms (Fig. 6).…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

“…In this regard, it is very interesting that several studies have shown that specific flavonoids can suppress the induction of iNOS gene and protein expression, and NO • production by cytokines and endotoxins in mouse macrophage RAW 264.7 cells [99,109,152]. The mechanism did not include a direct inhibitory effect on enzyme activity, but rather the modulation of cell signaling pathways necessary for NOS gene expression.…”

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

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MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

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Oxidative and nitrosative stress is increasingly associated with the pathology of neurodegeneration and aging. The molecular mechanisms underlying oxidative/nitrosative stress-induced neuronal damage are emerging and appear to involve a mode of death in which mitogen-activated protein kinase (MAPK) signaling pathways are strongly implicated. Thus, attention is turning towards the modulation of intracellular signaling as a therapeutic approach against neurodegeneration. Both endogenous and dietary agents have been suggested as potent modulators of intracellular signal transduction, e.g. nitric oxide and flavonoids, respectively. This review addresses recent findings on the biological effects of flavonoids and nitric oxide in neurodegeneration and aims to elucidate the rationale for their prospective use as modulators of cellular signal transduction. © 2002 Elsevier Science Inc. All rights reserved.Keywords: Apoptosis; Oxidative stress; Neuron; Flavonoids; MAP kinase; JNK; ERK; Epicatechin; Nitric oxide; Mitochondria; Redox status; Polyphenols Abbreviations: AKT, serine/threonine kinase (also known as protein kinase B); AP-1, activator protein-1; Apaf-1, apoptosis protease activating factor-1; ASK1, apoptosis signal-regulating kinase-1; Bad, Bcl-2/BclX Lassociated death promoting protein; Bax, pro-apoptotic protein of the Bcl-2 family; Bcl-2, B-cell lymphoma 2: protein with anti-apoptotic properties; BclX L , long form of Bclx: anti-apoptotic protein of the Bcl-2 family; Caspase, cysteinyl aspartic acid-protease; c-Jun, mammalian equivalent of Jun: part of the AP-1 transcription complex; CREB, cAMP response element binding protein; DIABLO/smac, mitochondria-related pro-apoptotic protein: inhibits XIAP; ERK1/2, extracellular signal-related kinase; Fas, CD95: member of the TNF receptor family; GSHST, glutathione Stransferase; JNK, c-Jun amino-terminal kinase; MAPK, mitogen-activated protein kinase; MAPKK, MAPK kinase; MAPKKK, MAPKK kinase; MEK1/2, ERK1/2-specific MAPKK; MKK4/7, JNK-specific MAPKK; MSK1, mitogen-and stress-activated kinase-1; NF-B, nuclear factor of immunoglobulin k locus in B-cells; ONOO − , peroxynitrite anion; p53, pro-apoptotic tumor suppressor gene product; PI3-kinase, phosphoinositol 3-kinase; Ras, small G-protein; RNS, reactive nitrogen species; ROS, reactive oxygen species; RSK, pp90 ribosomal S6 kinase; SAPK, stressactivated protein kinase; XIAP, X-linked inhibitor of apoptosis: inhibits the activation of caspase-9

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Section: Mapk Signaling Under Oxidative Stressmentioning

confidence: 99%

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

Section: Nitric Oxide and Mapk Signalingmentioning

confidence: 99%

See 2 more Smart Citations

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

Schroeter

Boyd

Spencer

et al. 2002

Neurobiology of Aging

308

178

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“…An increasing number of proteins have been found to undergo Snitrosylation in vivo [2][3][4]. For example, the inhibition of protein-tyrosine phosphatases by 5-nitrosylation is critical in regulating cellular signal transduction pathways [5]; similarly, S-nitrosylation can suppress C-Jun N-terminal kinase activation in intact cells [6]. On the other hand, S-nitrosylation of OxyR has been shown to activate OxyR-dependent transcriptional events [7], while S-nitrosylation of ryanodine receptor promotes its ability to release Ca 2 + from the sarcoplasmic reticulum [8].…”

mentioning

confidence: 99%

A strategy for direct identification of protein S-nitrosylation sites by quadrupole time-of-flight mass spectrometry

Wang

Liu

et al. 2008

J. Am. Soc. Mass Spectrom.

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S-nitrosylation of proteins serves an important role in regulating diverse cellular processes including signal transduction, DNA repair, and neurotransmission. Identification of Snitrosylation sites is crucial for understanding the significance of this post-translational modification (PTM) in modulating the function of a protein. However, it is challenging to identify S-nitrosylation sites directly by mass spectrometric (MS) methods due to the labile nature of the 5-NO bond. Here we describe a strategy for direct identification of protein S-nitrosylation sites in an electrospray ionization (ESI) quadrupole time-of-flight (QTOF) mass spectrometer without prior chemical derivatization of S-nitrosylated peptides. Both sample buffer composition and MS hardware parameters were carefully adjusted to ensure that S-nitrosylated peptide ions could be analyzed by the QTOF MS with optimal signal/noise ratios. It was crucial that the proteins were preserved in a sample solution containing 1 mM EDTA and 0.1 mM neocuproine at neutral pH. Proteins dissolved in this solution are amenable to in-solution tryptic digestion, which is important for the analysis of biological samples. S-nitrosylated peptides were effectively analyzed by LC/MS/MS on QTOF MS, with an optimized cone voltage of 20 V and collision energy of 4 V. We have successfully applied this method to thioredoxin, a key antioxidant protein, and identified within it an S-nitrosylation site at

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Analysis of Protein S‐Nitrosylation

Mannick

Schonhoff

2006

CP Protein Science

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S-nitrosylation is the binding of an NO group to a cysteine or other thiol. Like phosphorylation, S-nitrosylation is a precisely targeted and rapidly reversible post-translational modification that serves as an on/off switch for protein function during cell signaling. However, unlike phosphorylation, S-nitrosylation of proteins occurs nonenzymatically and is mediated, at least in part, by redox-regulated chemical reactions in cells. Alterations in pH, pO(2), cellular reductants, transition metals, and UV light lead to the loss and/or gain of S-NO bonds. Due to the redox-sensitive nature of the modification, analysis of protein S-nitrosylation is technically difficult, since the S-NO bond is easily disrupted during sample preparation. In addition, the level of S-nitrosylated proteins in cells approaches the limit of detection of currently available technology. Despite these technical challenges, several useful methods have been developed recently to measure protein S-nitrosylation in biological samples, and these are described in this unit.

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Nitric oxide negatively regulates c-Jun N-terminal kinase/stress-activated protein kinase by means ofS-nitrosylation

Cited by 229 publications

References 50 publications

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

A strategy for direct identification of protein S-nitrosylation sites by quadrupole time-of-flight mass spectrometry

Analysis of Protein S‐Nitrosylation

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