Decomposition of S-Nitrosocysteine via S- to N-Transnitrosation

Peterson, Lisa A.; Wagener, Tanja; Sies, Helmut; Stahl, Wilhelm

doi:10.1021/tx700095u

Cited by 24 publications

(22 citation statements)

References 16 publications

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“…Curiously, a recent report described activation of MMP-9 by selected concentrations of SPER-NO, which appears to counter our observations, although the mechanism of activation was not addressed (28). First, only high concentrations of an exceptionally reactive S-nitrosothiol, CSNO (29), were found to weakly activate proMMP9, consistent with earlier findings (4), but the biological significance of this is questionable because biological concentrations of SNO are in the nanomolar range (30). Second, although several diverse NO donors and S-nitro-sothiols are similarly capable of inducing S-nitrosylation within a peptide that represents the Cys-containing prodomain region of proMMP-9, the fact that most of these agents cannot activate proMMP-9 would suggest that S-nitrosylation may not be responsible for MMP-9 activation by CSNO or by other RNS (4,9).…”

Section: Discussioncontrasting

confidence: 85%

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

et al. 2008

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Matrix metalloproteases (MMPs) are Zn-containing endopeptidases involved in the degradation of extracellular matrix components and are typically secreted in a latent (pro-MMP) form and activated either by proteolytic or oxidative disruption of a conserved cysteine switch. Several recent studies have suggested that nitric oxide (NO) can contribute to the activation of MMPs, but the mechanisms involved are incompletely understood. We investigated the ability of NO to regulate the activation of (pro)MMP-9 using a variety of NO-donor compounds and characterized modifications of the cysteine switch using a synthetic peptide (PRCGVPDLGR) representing the cysteine switch domain of MMP-9. Among the NO-donors used, only S-nitrosocysteine (SNOC) was found to be capable of modest activation of proMMP-9, but S-nitrosoglutathione (GSNO) or the NONOates, DEA-NO, SPER-NO, or DETA-NO, were ineffective. In fact, high concentrations of DETA-NO were found to inhibit MMP-9 activity, presumably by direct interaction with the active-site Zn 2+ . Analysis of chemical modifications within the Cys-containing peptide, PRCGVPDLGR, revealed rapid and transient S-nitrosylation by SNOC and GSNO, and formation of mixed disulfides and dimerized peptide as major final products. Similarly, NONOates induced transient S-nitrosylation and primarily peptide dimerization. Coordination of the peptide Cys with a synthetic Zn 2+ complex, to more closely mimic the structure of the active site in proMMP-9, reduced peptide nitrosylation and oxidation by NONOates, but enhanced peptide nitrosylation by SNOC and GSNO. Collectively, our results demonstrate that NO is incapable of directly activating proMMP-9 and that S-nitrosylation of MMP-9 propeptide by NO-donors is unrelated to their ability to regulate MMP-9 activity.Matrix metalloproteinases (MMPs) comprise a family of zinc-containing endopeptidases and play important roles in development, inflammation, tissue injury and repair, and tumor biology (1,2). The MMP family consists of at least 26 members that share several structural characteristics including a highly conserved Cys-containing pro-peptide domain and a catalytic domain containing three His residues bound to a Zn(II) metal ion. MMPs are typically expressed at low levels in normal tissues, but in conditions of inflammation and/or tissue injury, MMP expression is generally increased by the action of pro-inflammatory † This work was supported by NIH research grants R01 HL074295 and R01 HL068865 (to A.vdV.), T32 ES07122 (training fellowship to S.M.M.), and P20 RR16462 (to the Vermont Genetics Network). Several recent studies have suggested that NO contributes to the activation of MMPs or related metalloproteinases by S-nitrosylation (often also referred to as S-nitrosation) of the pro-domain Cys residue. For example, MMP-9 activation in vivo was found to be associated with increased NOS activity, and the nitrosothiol S-nitrosocysteine is capable of activating pro-MMP-9 by a mechanism that appears to involve transnitrosylation (4,11). Similar...

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Section: Discussioncontrasting

confidence: 85%

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

et al. 2008

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“…1B). Similar exposure to CSNO resulted in a more transient loss of TER during the first 2–3 hrs, consistent with its limited chemical stability [25], and did not significantly enhance permeability to FITC-Dextran over 24 hrs (Fig. 1).…”

Section: Resultssupporting

confidence: 56%

Nitric oxide and airway epithelial barrier function: Regulation of tight junction proteins and epithelial permeability

Olson

Greul

Hristova

et al. 2009

Archives of Biochemistry and Biophysics

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Acute airway inflammation is associated with enhanced production of nitric oxide (NO • ) and altered airway epithelial barrier function, suggesting a role of NO • or its metabolites in epithelial permeability. While high concentrations of S-nitrosothiols disrupted transepithelial resistance (TER) and increased permeability in 16HBE14o-cells, no significant barrier disruption was observed by NONOates, in spite of altered distribution and expression of some TJ proteins. Barrier disruption of mouse tracheal epithelial (MTE) cell monolayers in response to inflammatory cytokines was independent of NOS2, based on similar effects in MTE cells from NOS2-/-mice and a lack of effect of the NOS2-inhibitor 1400W. Cell pre-incubation with LPS protected MTE cells from TER loss and increased permeability by H 2 O 2 , which was independent of NOS2. However, NOS2 was found to contribute to epithelial wound repair and TER recovery after mechanical injury. Overall, our results demonstrate that epithelial NOS2 is not responsible for epithelial barrier dysfunction during inflammation, but may contribute to restoration of epithelial integrity.

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“…The irradiated solutions were then analyzed using HPLC. It was found that disulfide was the major product in argon saturated solutions, in agreement with earlier reports [5][6][7][8][9]. Meanwhile, in aerated solutions, nitrite was also formed along with disulfide.…”

Section: Resultssupporting

confidence: 90%

“…S-Nitrosothiols (RSNO) are generally believed as the bio reservoir for nitric oxide (NO) in a biological system [1] and hence their various ways of decomposition are very relevant [2][3][4][5][6][7]. The bond dissociation energy for S-N bond is between 20 and 32 kcal mol −1 [8,9].…”

Section: Introductionmentioning

confidence: 99%

Decomposition of S‐Nitrosothiols Induced by UV and Sunlight

Veleeparampil

Aravind

Aravindakumar

2009

Advances in Physical Chemistry

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Photochemical release of nitric oxide (NO) from the S-nitroso derivatives of glutathione, L-cysteine, N-acetyl-L-cysteine, Lcysteinemethylester, D,L-penicillamine, N-acetyl-D,L-penicillamine, and N-acetylcysteamine has been investigated at neutral and acidic pH. The release of NO from RSNO is one of the key reactions that could be utilized in photodynamic therapy. The UV-VIS and HPLC analyses have shown that under argon saturated conditions, disulfide (RSSR) is the major product of UV as well as sunlight induced decomposition. While in aerated conditions, nitirite-the end product of the oxidation of NO-was also observed along with disulfide. The formation of thiyl radical as the intermediate was reconfirmed by laser flash photolysis. The initial rate of formation of NO was on the order of 10 −5 dm 3 mol −1 s −1 . The quantum yields of these reactions were in the range of 0.2-0.8. The high quantum yields observed in the photo induced release of NO from RSNO using both UV and sunlight demonstrate the potential application of these reactions in photodynamic therapy.

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Decomposition of S-Nitrosocysteine via S- to N-Transnitrosation

Cited by 24 publications

References 16 publications

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

Nitric Oxide Regulation of MMP-9 Activation and Its Relationship to Modifications of the Cysteine Switch

Nitric oxide and airway epithelial barrier function: Regulation of tight junction proteins and epithelial permeability

Decomposition of S‐Nitrosothiols Induced by UV and Sunlight

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