Generation of Cholesterol Carboxyaldehyde by the Reaction of Singlet Molecular Oxygen [O2 (1Δg)] as Well as Ozone with Cholesterol

Uemi, Miriam; Ronsein, Graziella Eliza; Miyamoto, Sayuri; Medeiros, Marisa H. G.; Mascio, Paolo Di

doi:10.1021/tx800447b

Cited by 64 publications

(95 citation statements)

References 78 publications

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“…Figure 5b shows cholesterol in pure CH 3 OH at a concentration of 725 μM. The peak at m/z 401 has been reported in previous literature as protonated 5-cholesten-3β-ol-7-one ( Figure 5a, structure of neutral in Scheme 1f), a well known COP [11,30]. This suggests that the peak at m/z 401 in the MALDI mass spectra represents a solution-based oxidation product.…”

Section: Solution Based Oxidationsupporting

confidence: 54%

“…Employing an internal calibration using known DHB and cholesterol fragmentation peaks, the accurate masses of the radical cation peaks were determined. [12] and Uemi et al [11] led to the deduction that solution oxidation products contain hydroperoxide structures (Scheme 1c and d). However, there is no source of molecular oxygen or peroxide in either the matrix or analyte when under the vacuum conditions of the mass spectrometer.…”

Section: Identification and Origin Of Oxidation Productsmentioning

confidence: 99%

“…The oxygen-mediated and radical-mediated oxidation pathways of cholesterol have been studied extensively [10][11][12]. Smith [12] has shown that oxidation of cholesterol via the excited singlet state molecular oxygen pathway implicates 3β-hydroxy-5α-cholest-6-ene-5-hydroperoxide and 7α-hydroperoxide, whereas oxidation via the free radical mechanism involves 7-peroxy radicals or 7-hydroperoxides.…”

Section: Introductionmentioning

confidence: 99%

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Laser-Induced Oxidation of Cholesterol Observed During MALDI-TOF Mass Spectrometry

McAvey

Guan

Fortier

et al. 2011

J. Am. Soc. Mass Spectrom.

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Conditions for the detection of three odd-electron cholesterol oxidation peaks were determined and these peaks were shown to be artifacts of the matrix-assisted laser desorption time of flight (MALDI-TOF) process. Matrix choice, solvent, laser intensity and cholesterol concentration were systematically varied to characterize the conditions leading to the highest signals of the radical cation peaks, and it was found that initial cholesterol solution concentration and resultant density of solid cholesterol on the MALDI target were important parameters in determining signal intensities. It is proposed that hydroxyl radicals, generated as a result of laser irradiation of the employed 2, 5-dihydroxybenzoic acid (DHB) matrix, initiate cholesterol oxidation on the MALDI target. An attempt to induce the odd-electron oxidation peaks by means of adding an oxidizing agent succeeded using an acetonitrile solution of DHB, cholesterol, and cumene hydroperoxide. Moreover, addition of free radical scavengers reduced the abundances of some oxidation products under certain conditions. These results are consistent with the mechanism of oxidation proposed herein involving laser-induced hydroxyl radical production followed by attack on neutral cholesterol. Hydroxyl radical production upon irradiation of dithranol matrix may also be responsible for generation of the same radical peaks observed from cholesterol in dithranol by an analogous mechanism.

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Section: Solution Based Oxidationsupporting

confidence: 54%

Section: Identification and Origin Of Oxidation Productsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Laser-Induced Oxidation of Cholesterol Observed During MALDI-TOF Mass Spectrometry

McAvey

Guan

Fortier

et al. 2011

J. Am. Soc. Mass Spectrom.

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“…This secosterol-A concentration was further increased upon activation with PMA, suggesting that human leukocytes within atherosclerotic tissues are activated to produce an ozone-like oxidant ( 10 ). However, it has been recently reported that secosterol-A and -B were generated in an ozone-independent mann er via the Hock-cleavage of 5 ␣ -hydroperoxy cholesterol, which can arise from the singlet oxygen ene reaction with cholesterol ( 13,14 ). Secosterol-B is formed easily under acidic conditions in organic solvents ( 13,14 ), whereas secosterol-A is either not formed at all or is a minor component in the aqueous buffer ( 9 ).…”

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway

Tomono

Miyoshi

Shiokawa

et al. 2011

Journal of Lipid Research

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myeloperoxidase-dependent pathway. J. Lipid Res. 2011. 52: 87-97. Supplementary key words secosterol • neutrophils • myeloperoxidase • infl ammationA reactive species with a chemical signature similar to that of ozone has been proposed to be generated by the antibody-catalyzed oxidation of water with singlet oxygen during the oxidative burst of activated human neutrophils and in infl amed tissues ( 1, 2 ). The formation of an ozonelike oxidant from singlet oxygen by neutrophils can be catalyzed not only by antibodies but also by amino acids such as tryptophan, methionine, and cysteine ( 3 ). To prove the formation of an ozone-like oxidant by neutrophils, previous studies used chemical reactions, such as the conversion of indigo carmine to isatin sulfonic acid or the oxidation of vinylbenzoic acid to 4-carboxybenzaldehyde. However, these reactions are not suffi ciently specifi c to ozone to conclude an ozone production by neutrophils ( 4, 5 ).Further evidence for ozone formation in vivo was based on the detection and formation of the cholesterol ozonolysis products 3 ␤ -hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A, also called atheronal-A) and its aldolization product 3 ␤ -hydroxy-5 ␤ -hydroxy-B-norcholestane-6 ␤ -carboxaldehyde (secosterol-B, also called atheronal-B) in human tissues. These secosterols were previously reported to be formed only by ozone among the various reactive oxygen species (ROS) such as singlet oxygen, superoxide anion, hydroxyl Abstract 3 ␤ -Hydroxy-5-oxo-5,6-secocholestan-6-al (sec osterol-A) and its aldolization product 3 ␤ -hydroxy-5 ␤ -hydroxy-B-norcholestane-6 ␤ -carboxaldehyde (secosterol-B) were recently detected in human atherosclerotic tissues and brain specimens, and they may play pivotal roles in the pathogenesis of atherosclerosis and neurodegenerative diseases. However, as their origin remains unidentifi ed, we examined the formation mechanism, the stability, and the fate of secosterols in vitro and in vivo. About 40% of secosterol-A remained unchanged after 3 h incubation in the FBS-free medium, whereas 20% and 40% were converted to its aldehyde-oxidation product, 3 ␤ -hydroxy-5-oxo-secocholestan-6-oic acid, and secosterol-B, respectively. In the presence of FBS, almost all secosterol-A was converted immediately to these compounds. Secosterol-B in the medium, with and without FBS, was relatively stable, but ‫ف‬ 30% was converted to its aldehyde-oxidation product, 3 ␤ -hydroxy-5 ␤ -hydroxy-B-norcholestane-6-oic acid (secoB-COOH). When neutrophillike differentiated human leukemia HL-60 (nHL-60) cells activated with PMA were cultured in the FBS-free medium containing cholesterol, signifi cantly increased levels of secosterol-A and its aldehyde-oxidation product, but not secosterol-B, were formed. This secosterol-A formation was decreased in the culture of PMA-activated nHL-60 cells containing several reactive oxygen species (ROS) inhibitors and scavengers or in the culture of PMA-activated neutrophils isolated from myeloperoxidase (MPO)-defi cient mice. Our results demonst...

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“…Although the mechanisms of formation of secosterol-A and -B and their oxidized derivatives in vivo are not completely understood, secosterol-A and -B have been also reported to be formed in an ozone-independent manner in organic solvents via Hock-cleavage of 5-hydroperoxy cholesterol, which can arise from the singlet oxygen ene reaction with cholesterol. 5,6) We also found that secosterol-B rather than secosterol-A was preferentially formed in an in vitro reaction of cholesterol and singlet oxygen. 7) On the other hand, Wentworth et al reported recently that only ozone can react with cholesterol to form secosterol-A in aqueous solution, and that other oxidants, such as singlet oxygen, form secosterol-B as a major product, but not -A.…”

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confidence: 59%

Cytotoxic Effects of Secosterols and Their Derivatives on Several Cultured Cells

Tomono

Yasue

Miyoshi

et al. 2013

Bioscience, Biotechnology, and Biochemistry

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Generation of Cholesterol Carboxyaldehyde by the Reaction of Singlet Molecular Oxygen [O₂ (¹Δ_g)] as Well as Ozone with Cholesterol

Cited by 64 publications

References 78 publications

Laser-Induced Oxidation of Cholesterol Observed During MALDI-TOF Mass Spectrometry

Laser-Induced Oxidation of Cholesterol Observed During MALDI-TOF Mass Spectrometry

Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway

Cytotoxic Effects of Secosterols and Their Derivatives on Several Cultured Cells

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