A novel high resolution MS approach for the screening of 4-hydroxy-trans-2-nonenal sequestering agents

Colzani, Mara; Criscuolo, Angela; Maddis, Danilo De; Garzon, Davide; Yeum, Kyung‐Jin; Vistoli, Giulio; Carini, Marina; Aldini, Giancarlo

doi:10.1016/j.jpba.2013.12.024

Cited by 17 publications

(22 citation statements)

References 28 publications

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“…Sodium dihydrophosphate (NaH 2 PO 4 ·H 2 O), disodium phosphate (Na 2 HPO 4 ·2H 2 O), ammonium bicarbonate (NH 4 HCO 3 . [17] Analytical methods For each experiment, fresh 4-hydroxy-2nonenal was prepared as previously described.…”

Section: Methodsmentioning

confidence: 99%

“…[17] Briefly,u biquitin solution (40 mL) recovered from filter units was mixed with denaturing solution (40 mL) (H 2 O/CH 3 CN/HCOOH;4 0/60/0.2 v/v/v). [17] Briefly,u biquitin solution (40 mL) recovered from filter units was mixed with denaturing solution (40 mL) (H 2 O/CH 3 CN/HCOOH;4 0/60/0.2 v/v/v).…”

Section: Inhibition Of Carbonylation:inv Itro Incubation and Msbased mentioning

confidence: 99%

“…Quantification of the extent of carbonylation:Adedicated Xcalibur processing method was set to quantify the area under the + 11 multicharged peaks, [17] The percentage of modified ubiquitin obtained upon co-incubation with RCS and carbonyl quenchers was normalized against the percentage of modified ubiquitin obtained in the control samples (ubiquitin incubated with RCS without any quencher). The noise present in the blank sample (ubiquitin incubated without RCS) was subtracted.…”

Section: Inhibition Of Carbonylation:inv Itro Incubation and Msbased mentioning

confidence: 99%

“…The rationale of using ubiquitin as am odel protein wasr ecently described; [17,18] notably,t he lack of cysteine residues in the sequenceo fthis protein allows the observation of av ariety of RCS-derived modifications on different nucleophilicr esidues (i.e.,l ysine, arginine, and histidine), which would otherwise be maskedo rf lattened by the high reactivity of cysteine. In the present paper,t he ability of l-carnosine, hydralazine, pyridoxamine, and aminoguanidinet od osedependently inhibitt he protein carbonylation of ubiquitin induced by four different RCS-4-hydroxynonenal (HNE), methylglyoxal (MGO), glyoxal (GO), and malondialdehyde (MDA)-is compareda nd rationalizedi nt erms of density functional theory (DFT)-based quantum-mechanicald escriptors.…”

Section: Introductionmentioning

confidence: 99%

“…In the present paper,t he ability of l-carnosine, hydralazine, pyridoxamine, and aminoguanidinet od osedependently inhibitt he protein carbonylation of ubiquitin induced by four different RCS-4-hydroxynonenal (HNE), methylglyoxal (MGO), glyoxal (GO), and malondialdehyde (MDA)-is compareda nd rationalizedi nt erms of density functional theory (DFT)-based quantum-mechanicald escriptors. The rationale of using ubiquitin as am odel protein wasr ecently described; [17,18] notably,t he lack of cysteine residues in the sequenceo fthis protein allows the observation of av ariety of RCS-derived modifications on different nucleophilicr esidues (i.e.,l ysine, arginine, and histidine), which would otherwise be maskedo rf lattened by the high reactivity of cysteine. [19] Moreover ac omprehensive study on the reaction products generated in vitro by the incubation of RCS and sequestering agents (as detected by high-resolutionm ass spectrometry,H RMS) is also provided,t ogether with the reaction mechanisms leading to their formation.…”

Section: Introductionmentioning

confidence: 99%

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Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study

et al. 2016

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Reactive carbonyl species (RCS) are endogenous or exogenous byproducts involved in the pathogenic mechanisms of different oxidative-based disorders. Detoxification of RCS by carbonyl quenchers is a promising therapeutic strategy. Among the most studied quenchers are aminoguanidine, hydralazine, pyridoxamine, and carnosine; their quenching activity towards four RCS (4-hydroxy-trans-2-nonenal, methylglyoxal, glyoxal, and malondialdehyde) was herein analyzed and compared. Their ability to prevent protein carbonylation was evaluated in vitro by using an innovative method based on high-resolution mass spectrometry (HRMS). The reactivity of the compounds was RCS dependent: carnosine efficiently quenched 4-hydroxy-trans-2-nonenal, pyridoxamine was particularly active towards malondialdehyde, aminoguanidine was active towards methylglyoxal and glyoxal, and hydralazine efficiently quenched all RCS. Reaction products were generated in vitro and were characterized by HRMS. Molecular modeling studies revealed that the reactivity was controlled by specific stereoelectronic parameters that could be used for the rational design of improved carbonyl quenchers.

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Section: Methodsmentioning

confidence: 99%

Section: Inhibition Of Carbonylation:inv Itro Incubation and Msbased mentioning

confidence: 99%

Section: Inhibition Of Carbonylation:inv Itro Incubation and Msbased mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study

et al. 2016

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Effects of covalent modification by 4‐hydroxy‐2‐nonenal on the noncovalent oligomerization of ubiquitin

Grasso

Axelsen

2016

J. Mass Spectrom.

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When lipid membranes containing ω-6 polyunsaturated fatty acyl chains are subjected to oxidative stress, one of the reaction products is 4-hydroxy-2-nonenal (HNE) – a chemically reactive short chain alkenal that can covalently modify proteins. The ubiquitin proteasome system is involved in the clearing of proteins modified by oxidation products such as HNE, but the chemical structure, stability and function of ubiquitin may be impaired by HNE modification. To evaluate this possibility, the susceptibility of ubiquitin to modification by HNE has been characterized over a range of concentrations where ubiquitin forms non-covalent oligomers. Results indicate that HNE modifies ubiquitin at only two of the many possible sites, and that HNE modification at these two sites alters the ubiquitin oligomerization equilibrium. These results suggest that any role ubiquitin may have in clearing proteins damaged by oxidative stress may itself be impaired by oxidative lipid degradation products.

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Quenching activity of carnosine derivatives towards reactive carbonyl species: Focus on α−(methylglyoxal) and β−(malondialdehyde) dicarbonyls

Vistoli

Colzani

Mazzolari

et al. 2017

Biochemical and Biophysical Research Communications

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A novel high resolution MS approach for the screening of 4-hydroxy-trans-2-nonenal sequestering agents

Cited by 17 publications

References 28 publications

Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study

Reactivity, Selectivity, and Reaction Mechanisms of Aminoguanidine, Hydralazine, Pyridoxamine, and Carnosine as Sequestering Agents of Reactive Carbonyl Species: A Comparative Study

Effects of covalent modification by 4‐hydroxy‐2‐nonenal on the noncovalent oligomerization of ubiquitin

Quenching activity of carnosine derivatives towards reactive carbonyl species: Focus on α−(methylglyoxal) and β−(malondialdehyde) dicarbonyls

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