Discovery and microassay of a nitrite-dependent carbonic anhydrase activity by stable-isotope dilution gas chromatography–mass spectrometry

Zinke, Maximilian; Hanff, Erik; Böhmer, Anke; Supuran, Claudiu T.; Tsikas, Dimitrios

doi:10.1007/s00726-015-2081-3

Cited by 19 publications

(18 citation statements)

References 33 publications

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“…Nitrate is able to bind to carbonic anhydrase active site [ 104 ], but not it cannot be utilized to form S-nitrosothiols as nitrite can be [ 105 ]. It can inhibit platelet aggregation in whole blood, but the mechanism remains unclear [ 101 ].…”

Section: Platelet Carbonic Anhydrasementioning

confidence: 99%

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Jakubowski

Szahidewicz-Krupska

Doroszko

2018

BioMed Research International

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Carbonic anhydrases constitute a group of enzymes that catalyse reversible hydration of carbon dioxide leading to the formation of bicarbonate and proton. The platelet carbonic anhydrase II (CAII) was described for the first time in the '80s of the last century. Nevertheless, its direct role in platelet physiology and pathology still remains poorly understood. The modulation of platelet CAII action as a therapeutic approach holds promise as a novel strategy to reduce the impact of cardiovascular diseases. This short review paper summarises the current knowledge regarding the role of human CAII in regulating platelet function. The potential future directions considering this enzyme as a potential drug target and important pathophysiological chain in platelet-related disorders are described.

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Section: Platelet Carbonic Anhydrasementioning

confidence: 99%

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Jakubowski

Szahidewicz-Krupska

Doroszko

2018

BioMed Research International

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“…As CA inhibitors may have unknown off‐target effects due to different tissue specific isozymes expression (Swenson, 2016), the CAII deficient mouse model allowed us to characterize the function of CAII in nitrite signalling, on a relatively clean background. Although renal carbonic anhydrases (CAII and CAIV) are involved in the reabsorption of endogenous nitrite (Chobanyan‐Jürgens et al, 2012; Zinke et al, 2016), we examined the effect of CAII KO on endogenous nitrite levels in urine and no differences were detected among CAII −/− , CAII +/− , and wild‐type mice. Our assessment of levels of plasma nitrite support this finding with similar nitrite levels across the genotypes (Figure S2).…”

Section: Discussionmentioning

confidence: 99%

“…Haemoglobin (Basu et al, 2007), nitrophorin (He & Knipp, 2009), and the zinc‐containing carbonic anhydrase (CA) II (Aamand et al, 2009b) have been reported to exhibit nitrite anhydrase activities. However, the role of CAII in nitrite‐dependent NO formation remains controversial as a number of studies have been unable to detect changes in measured NO formation from nitrite with red blood cells (Liu et al, 2015) and in vivo after treatment with CA inhibitors (Andring et al, 2018; Pickerodt et al, 2018; Zinke, Hanff, Böhmer, Supuran, & Tsikas, 2016).…”

Section: Introductionmentioning

confidence: 99%

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Carbonic anhydrase II does not regulate nitrite‐dependent nitric oxide formation and vasodilation

Sparacino-Watkins

Wang

Wajih

et al. 2019

British J Pharmacology

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Background and purpose Although it has been reported that bovine carbonic anhydrase CAII is capable of generating NO from nitrite, the function and mechanism of CAII in nitrite‐dependent NO formation and vascular responses remain controversial. We tested the hypothesis that CAII catalyses NO formation from nitrite and contributes to nitrite‐dependent inhibition of platelet activation and vasodilation. Experiment approach The role of CAII in enzymatic NO generation was investigated by measuring NO formation from the reaction of isolated human and bovine CAII with nitrite using NO photolysis‐chemiluminescence. A CAII‐deficient mouse model was used to determine the role of CAII in red blood cell mediated nitrite reduction and vasodilation. Key results We found that the commercially available purified bovine CAII exhibited limited and non‐enzymatic NO‐generating reactivity in the presence of nitrite with or without addition of the CA inhibitor dorzolamide; the NO formation was eliminated with purification of the enzyme. There was no significant detectable NO production from the reaction of nitrite with recombinant human CAII. Using a CAII‐deficient mouse model, there were no measurable changes in nitrite‐dependent vasodilation in isolated aorta rings and in vivo in CAII−/−, CAII+/−, and wild‐type mice. Moreover, deletion of the CAII gene in mice did not block nitrite reduction by red blood cells and the nitrite‐NO‐dependent inhibition of platelet activation. Conclusion and implications These studies suggest that human, bovine and mouse CAII are not responsible for nitrite‐dependent NO formation in red blood cells, aorta, or the systemic circulation.

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“…The origin of endogenous CysSNO is unclear. CysSNO can be formed from CysSH and higher oxides of NO including nitrous acid (HONO) and its anhydride (N 2 O 3 ) [28] , [29] .…”

Section: Introduction Of No and S -Nitrosothiolsmentioning

confidence: 99%

S-Nitroso-N-acetyl-L-cysteine ethyl ester (SNACET) and N-acetyl-L-cysteine ethyl ester (NACET)–Cysteine-based drug candidates with unique pharmacological profiles for oral use as NO, H2S and GSH suppliers and as antioxidants: Results and overview

Tsikas

Schwedhelm

Surdacki

et al. 2018

Journal of Pharmaceutical Analysis

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S-Nitrosothiols or thionitrites with the general formula RSNO are formally composed of the nitrosyl cation (NO+) and a thiolate (RS−), the base of the corresponding acids RSH. The smallest S-nitrosothiol is HSNO and derives from hydrogen sulfide (HSH, H2S). The most common physiological S-nitrosothiols are derived from the amino acid L-cysteine (CysSH). Thus, the simplest S-nitrosothiol is S-nitroso-L-cysteine (CysSNO). CysSNO is a spontaneous potent donor of nitric oxide (NO) which activates soluble guanylyl cyclase to form cyclic guanosine monophosphate (cGMP). This activation is associated with multiple biological actions that include relaxation of smooth muscle cells and inhibition of platelet aggregation. Like NO, CysSNO is a short-lived species and occurs physiologically at concentrations around 1 nM in human blood. CysSNO can be formed from CysSH and higher oxides of NO including nitrous acid (HONO) and its anhydride (N2O3). The most characteristic feature of RSNO is the S-transnitrosation reaction by which the NO+ group is reversibly transferred to another thiolate. By this way numerous RSNO can be formed such as the low-molecular-mass S-nitroso-N-acetyl-L-cysteine (SNAC) and S-nitroso-glutathione (GSNO), and the high-molecular-mass S-nitrosol-L-cysteine hemoglobin (HbCysSNO) present in erythrocytes and S-nitrosol-L-cysteine albumin (AlbCysSNO) present in plasma at concentrations of the order of 200 nM. All above mentioned RSNO exert NO-related biological activity, but they must be administered intravenously. This important drawback can be overcome by lipophilic charge-free RSNO. Thus, we prepared the ethyl ester of SNAC, the S-nitroso-N-acetyl-L-cysteine ethyl ester (SNACET), from synthetic N-acetyl-L-cysteine ethyl ester (NACET). Both NACET and SNACET have improved pharmacological features over N-acetyl-L-cysteine (NAC) and S-nitroso-N-acetyl-L-cysteine (SNAC), respectively, including higher oral bioavailability. SNACET exerts NO-related activities which can be utilized in the urogenital tract and in the cardiovascular system. NACET, with high oral bioavailability, is a strong antioxidant and abundant precursor of GSH, unlike its free acid N-acetyl-L-cysteine (NAC). Here, we review the chemical and pharmacological properties of SNACET and NACET as well as their analytical chemistry. We also report new results from the ingestion of S-[15N]nitroso-N-acetyl-L-cysteine ethyl ester (S15NACET) demonstrating the favorable pharmacological profile of SNACET.

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Discovery and microassay of a nitrite-dependent carbonic anhydrase activity by stable-isotope dilution gas chromatography–mass spectrometry

Cited by 19 publications

References 33 publications

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

The Human Carbonic Anhydrase II in Platelets: An Underestimated Field of Its Activity

Carbonic anhydrase II does not regulate nitrite‐dependent nitric oxide formation and vasodilation

S-Nitroso-N-acetyl-L-cysteine ethyl ester (SNACET) and N-acetyl-L-cysteine ethyl ester (NACET)–Cysteine-based drug candidates with unique pharmacological profiles for oral use as NO, H2S and GSH suppliers and as antioxidants: Results and overview

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