SNO-ing at the Nociceptive Synapse?

Tegeder, Irmgard; Scheving, Reynir; Wittig, Ilka; Geißlinger, Gerd

doi:10.1124/pr.110.004200

Cited by 52 publications

(35 citation statements)

References 276 publications

(292 reference statements)

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“…MAPK activation also mediates proinflammatory signaling pathways and, importantly in the context of the observations made above, proinflammatory cytokine production [147]. Hence, the inhibition of MAPK by S-nitrosylation [148] could have profound effects on the immune response. Snitrosylation appears to inhibit the MAPK signaling cascade at two levels.…”

Section: Role Of Nitrosylation On the Immune Response Nitrosylation Amentioning

confidence: 96%

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Morris¹,

Berk

Klein

et al. 2016

Mol Neurobiol

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Nitric oxide plays an indispensable role in modulating cellular signaling and redox pathways. This role is mainly effected by the readily reversible nitrosylation of selective protein cysteine thiols. The reversibility and sophistication of this signaling system is enabled and regulated by a number of enzymes which form part of the thioredoxin, glutathione, and pyridoxine antioxidant systems. Increases in nitric oxide levels initially lead to a defensive increase in the number of nitrosylated proteins in an effort to preserve their function. However, in an environment of chronic oxidative and nitrosative stress (O&NS), nitrosylation of crucial cysteine groups within key enzymes of the thioredoxin, glutathione, and pyridoxine systems leads to their inactivation thereby disabling denitrosylation and transnitrosylation and subsequently a state described as "hypernitrosylation." This state leads to the development of pathology in multiple domains such as the inhibition of enzymes of the electron transport chain, decreased mitochondrial function, and altered conformation of proteins and amino acids leading to loss of immune tolerance and development of autoimmunity. Hypernitrosylation also leads to altered function or inactivation of proteins involved in the regulation of apoptosis, autophagy, proteomic degradation, transcription factor activity, immune-inflammatory pathways, energy production, and neural function and survival. Hypernitrosylation, as a consequence of chronically elevated O&NS and activated immune-inflammatory pathways, can explain many characteristic abnormalities observed in neuroprogressive disease including major depression and chronic fatigue syndrome/myalgic encephalomyelitis. In those disorders, increased bacterial translocation may drive hypernitrosylation and autoimmune responses against nitrosylated proteins.

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Section: Role Of Nitrosylation On the Immune Response Nitrosylation Amentioning

confidence: 96%

Nitrosative Stress, Hypernitrosylation, and Autoimmune Responses to Nitrosylated Proteins: New Pathways in Neuroprogressive Disorders Including Depression and Chronic Fatigue Syndrome

Morris¹,

Berk

Klein

et al. 2016

Mol Neurobiol

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“…Despite some evidence indicating a possible role for the compartmentalization of iNOS and short-range actions of high levels of NO in protein S-nitrosylation-for instance, in the S-nitrosylation of matrix metalloproteinase 9 (MMP-9) at the leading edge of migrating cells, and chloride intracellular channel 4 (CLIC4) during its nuclear translocation in macrophages (58, 99)-eNOS and neuronal nitric oxide synthase (nNOS) are the prototypic NOS whose dependence between localization and S-nitrosylation has been more extensively studied (70,151).…”

Section: Regulation Of S-nitrosylation By Subcellular Localization Ofmentioning

confidence: 99%

“…The increase in AMPA receptors at the synapse makes the synapse respond with larger excitatory currents upon synaptic stimulation, thus making the synapse stronger. Several intracellular proteins are involved in the recruitment of AMPA receptors to the synaptic membrane, and some may be functionally S-nitrosylated (4,115,151).…”

Section: S-nitrosylation and Synaptic Plasticitymentioning

confidence: 99%

Specificity in S-Nitrosylation: A Short-Range Mechanism for NO Signaling?

Martínez‐Ruiz

Araújo²,

Izquierdo-Álvarez³

et al. 2013

Antioxidants & Redox Signaling

109

104

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Significance: Nitric oxide (NO) classical and less classical signaling mechanisms (through interaction with soluble guanylate cyclase and cytochrome c oxidase, respectively) operate through direct binding of NO to protein metal centers, and rely on diffusibility of the NO molecule. S-Nitrosylation, a covalent post-translational modification of protein cysteines, has emerged as a paradigm of nonclassical NO signaling. Recent Advances: Several nonenzymatic mechanisms for S-nitrosylation formation and destruction have been described. Enzymatic mechanisms for transnitrosylation and denitrosylation have been also studied as regulators of the modification of specific subsets of proteins. The advancement of modification-specific proteomic methodologies has allowed progress in the study of diverse S-nitrosoproteomes, raising clues and questions about the parameters for determining the protein specificity of the modification. Critical Issues: We propose that S-nitrosylation is mainly a short-range mechanism of NO signaling, exerted in a relatively limited range of action around the NO sources, and tightly related to the very controlled regulation of subcellular localization of nitric oxide synthases. We review the nonenzymatic and enzymatic mechanisms that support this concept, as well as physiological examples of mammalian systems that illustrate well the precise compartmentalization of S-nitrosylation. Future Directions: Individual and proteomic studies of protein S-nitrosylation-based signaling should take into account the subcellular localization in order to gain further insight into the functional role of this modification in (patho)physiological settings.

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“…The current understanding of NO mediated effects in nociceptive and nerve injury models suggests that glutamate release from the injured or stimulated afferent neurons activates NMDA receptors of the postsynaptic neurons which is linked to activation of neuronal NOS in the postsynaptic density and subsequent NO release. NO may then act on several targets in its vicinity [2,33]. This idea is supported by the observed increase of protein S-nitrosylation after sciatic nerve injury which was in part reversible upon treatment with L-NAME and paralleled by L-NAME mediated reversal of hyperalgesia.…”

Section: Discussionmentioning

confidence: 64%