Nitro-fatty acids in cardiovascular regulation and diseases characteristics and molecular mechanisms

Villacorta, Luis; Gao, Zhen; Schöpfer, Francisco J.; Freeman, Bruce Α.; Chen, Y. Eugene

doi:10.2741/4425

Cited by 45 publications

(36 citation statements)

References 108 publications

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“…Results obtained in animal systems have shown that nitroalkylation of specific anti-inflammatory and antioxidant-related proteins leads to the modification of their activities, thus promoting important beneficial mechanisms [2], [7]. Due to there is no information available concerning this PTM in plants, analyzing this capacity with key components of antioxidant pathways could be useful to understand the mechanism of action of NO 2 -FAs in plant systems.…”

Section: Signaling Role Of No2-ln In Plant Physiologymentioning

confidence: 99%

“…Numerous studies have since reported a selective nitration of fatty acids under physiological conditions, highlighting the greater susceptibility to nitration of conjugated fatty acids than methyl-interrupted dienes or polyenes in animal systems [5]. Most of these analyses have shown that these molecules trigger pleiotropic signaling actions including a remarkable anti-inflammatory and antioxidant response [6], [7], [8], [9]. A measurable increase in the levels of NO 2 -FAs has been shown under different pathological conditions such as ischemia reperfusion injury or after LPS injection in the peritoneum [1], [10].…”

Section: Introductionmentioning

confidence: 99%

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Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism

et al. 2017

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Recent studies in animal systems have shown that NO can interact with fatty acids to generate nitro-fatty acids (NO2-FAs). They are the product of the reaction between reactive nitrogen species and unsaturated fatty acids, and are considered novel mediators of cell signaling based mainly on a proven anti-inflammatory response. Although these signaling mediators have been described widely in animal systems, NO2-FAs have scarcely been studied in plants. Preliminary data have revealed the endogenous presence of free and protein-adducted NO2-FAs in extra-virgin olive oil (EVOO), which appear to be contributing to the cardiovascular benefits associated with the Mediterranean diet. Importantly, new findings have displayed the endogenous occurrence of nitro-linolenic acid (NO2-Ln) in the model plant Arabidopsis thaliana and the modulation of NO2-Ln levels throughout this plant's development. Furthermore, a transcriptomic analysis by RNA-seq technology established a clear signaling role for this molecule, demonstrating that NO2-Ln was involved in plant-defense response against different abiotic-stress conditions, mainly by inducing the chaperone network and supporting a conserved mechanism of action in both animal and plant defense processes. Thus, NO2-Ln levels significantly rose under several abiotic-stress conditions, highlighting the strong signaling role of these molecules in the plant-protection mechanism. Finally, the potential of NO2-Ln as a NO donor has recently been described both in vitro and in vivo. Jointly, this ability gives NO2-Ln the potential to act as a signaling molecule by the direct release of NO, due to its capacity to induce different changes mediated by NO or NO-related molecules such as nitration and S-nitrosylation, or by the electrophilic capacity of these molecules through a nitroalkylation mechanism. Here, we describe the current state of the art regarding the advances performed in the field of NO2-FAs in plants and their implication in plant physiology.

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Section: Signaling Role Of No2-ln In Plant Physiologymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism

et al. 2017

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“…These NO 2 and N 2 O 3 -generating reactions are also likely to produce nitro-fatty acids (14,154,193,194) in the RBC membrane. Nitro-fatty acid derivatives of oleic acid have been found in RBC membranes (15).…”

Section: Preserving Transporting and Delivering Hb-derived Nox Bioamentioning

confidence: 99%

“…Production of the NO 2 radical at a moderate rate is likely to be anti-inflammatory, in that it can both regenerate free NO by oxidizing HbNO to form met Hb plus NO (20) and help generate nitro-fatty acids, which have impressive antiinflammatory properties (8,58,194). NO 2 is also produced via the complex reaction of nitrite with oxyHb in a reaction that involves ferryl formation (77,91,135).…”

Section: The Interplay Of Reduced Nox Generation and Enhanced Ferryl mentioning

confidence: 99%

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

Hirsch

Sibmooh

Fucharoen

et al. 2017

Antioxidants & Redox Signaling

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Significance: Oxidative stress and generation of free radicals are fundamental in initiating pathophysiological mechanisms leading to an inflammatory cascade resulting in high rates of morbidity and death from many inherited point mutation-derived hemoglobinopathies. Hemoglobin (Hb)E is the most common point mutation worldwide. The b E -globin gene is found in greatest frequency in Southeast Asia, including Thailand, Malaysia, Indonesia, Vietnam, Cambodia, and Laos. With the wave of worldwide migration, it is entering the gene pool of diverse populations with greater consequences than expected. Critical Issues: While HbE by itself presents as a mild anemia and a single gene for b-thalassemia is not serious, it remains unexplained why HbE/b-thalassemia (HbE/b-thal) is a grave disease with high morbidity and mortality. Patients often exhibit defective physical development, severe chronic anemia, and often die of cardiovascular disease and severe infections. Recent Advances: This article presents an overview of HbE/b-thal disease with an emphasis on new findings pointing to pathophysiological mechanisms derived from and initiated by the dysfunctional property of HbE as a reduced nitrite reductase concomitant with excess a-chains exacerbating unstable HbE, leading to a combination of nitric oxide imbalance, oxidative stress, and proinflammatory events. Future Directions: Additionally, we present new therapeutic strategies that are based on the emerging molecular-level understanding of the pathophysiology of this and other hemoglobinopathies. These strategies are designed to short-circuit the inflammatory cascade leading to devastating chronic morbidity and fatal consequences. Antioxid. Redox Signal. 26,[794][795][796][797][798][799][800][801][802][803][804][805][806][807][808][809][810][811][812][813]

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“…[7] Nitro-fatty acids (NO 2 -FA) have been found both in vitro and in vivo, namely in red blood cells, [8,9] plasma, [8][9][10][11] and in different tissues, either in normal or in inflammatory conditions. [12] Several published works described the NO 2 -FA adducts with GSH, [13,14] GAPDH, [13,14] NF-κB, [15] and PPARγ. [16] This type of post-translational modification seems to be an important regulatory pathway for the modulation of enzymatic activity, redox homeostasis, and in signaling events [7,13,17] associated with inhibition of inflammatory process and pro-survival responses.…”

Section: Introductionmentioning

confidence: 99%

Characterization of Nitrophospholipid‐Peptide Covalent Adducts by Electrospray Tandem Mass Spectrometry: A First Screening Analysis Using Different Instrumental Platforms

Montero-Bullón

Melo

Domingues

et al. 2018

Euro J Lipid Sci & Tech

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Lipids are well‐known targets of reactive nitrogen species and this reaction leads to the formation of nitrated lipids that have been associated with anti‐inflammatory and cytoprotective effects. Nitro‐fatty acids (NO2‐FA) are highly electrophilic compounds that can form covalent adducts with proteins, leading to the formation of lipoxidation adducts, which modulate the protein structure and function. Nitrated phospholipids (NO2‐PL) have been detected recently in biological samples, but their biological effects are unknown, although similarly to what has been described for nitrated lipids, it has been hypothesized that they may react with peptides and proteins. In this study, in vitro biomimetic assays are used to synthetize adducts of nitrated POPC (NO2POPC), already detected in biological samples, and GSH peptide. The formation of NO2POPC‐GSH adducts is studied by ESI‐MS and MS2, using both low and high energy CID in different MS platforms: a LXQ linear ion trap, a Q‐TOF 2, and a Q‐Exactive Hybrid Quadrupole‐Orbitrap. Typical product ions observed under MS2 conditions are modified b, y, and C ions bearing NO2POPC covalently linked that unequivocally confirms the presence of the lipid‐peptide adduct. Typical loss of HNO2 is only observed in the MS2 of the mono‐charged precursor ions, [M+H]+. Product ions at m/z 184 or neutral loss of 183 Da are assigned as typical fragmentations that confirm the presence of the phosphatidylcholine. In summary, the characterization of nitro PL‐peptide adducts by MS and MS2 allows the identification of the structure and specific MS2 reporter ions to be used to pinpoint these adductions in biological systems. Practical Applications: The covalent interaction between nitro phospholipids and peptides suggests a new pathway in cellular transduction of nitroxidative stress signal. This adduction can be considered a post‐translational modification (PTM) of lipoxidation type, similarly as it has been described for nitro‐fatty acids and with important physiological implications. The identification and characterization of the nitro phospholipids and peptides adducts are possible by MS and tandem MS. This analytical technique also represents a robust and sensitive approach for detection of nitro‐lipids adduction to peptides or proteins in biological samples, allowing to disclose their physiological and clinical implications. Tandem MS fingerprinting is an essential feature for this purpose, so in this work, the identification of the reporter ions typical for this type of lipoxidation adducts is provided. These reporter ions can be used to design target (NL, PIS, or MRM) approaches to detect these type of PTM in biological environments. Nitrated phospholipids can adduct covalently to nucleophilic peptide gluthathione, as demonstrated by characterization using tandem MS.

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Nitro-fatty acids in cardiovascular regulation and diseases characteristics and molecular mechanisms

Cited by 45 publications

References 108 publications

Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism

Nitro-fatty acids in plant signaling: New key mediators of nitric oxide metabolism

HbE/β-Thalassemia and Oxidative Stress: The Key to Pathophysiological Mechanisms and Novel Therapeutics

Characterization of Nitrophospholipid‐Peptide Covalent Adducts by Electrospray Tandem Mass Spectrometry: A First Screening Analysis Using Different Instrumental Platforms

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