Formation of cholesterol ozonolysis products through an ozone-free mechanism mediated by the myeloperoxidase–H2O2–chloride system

Tomono, Susumu; Miyoshi, Noriyuki; Sato, Kazuaki; Ohba, Yusuke; Ohshima, Hiroshi

doi:10.1016/j.bbrc.2009.03.155

Cited by 31 publications

(31 citation statements)

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“…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 ). We reported recently that almost equal amounts of secosterol-A and -B were formed by the reaction of cholesterol with human myeloperoxidase (MPO) in the presence of its substrates hydrogen peroxide (H 2 O 2 ) and Cl Ϫ ( 15 ). On the other hand, fi ve times more secosterol-B was formed than secosterol-A when cholesterol was incubated with hypochlorous acid (HOCl) and hydrogen peroxide.…”

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

“…On the other hand, fi ve times more secosterol-B was formed than secosterol-A when cholesterol was incubated with hypochlorous acid (HOCl) and hydrogen peroxide. However, in both the reactions, immunoglobulin G (IgG) did not enhance the formation of secosterols, suggesting that singlet oxygen ( 1 O 2 ) and possibly another oxidant, but not an ozone-like oxidant, mediated the formation of secosterols ( 15 ).…”

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

“…We recently reported a highly sensitive method for the quantifi cation of secosterols based on derivatization with fl uorescent dansyl hydrazine (DH) and detection by LC-MS/MS system, in which both secosterols were confi rmed to be stable during the derivatization process ( 15 ). This sensitive method has allowed us to perform quantitative analysis of secosterols in cell culture and in animal tissues.…”

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

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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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Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

Section: Formation Of Secosterols By Hl-60 Cellsmentioning

confidence: 99%

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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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“…Compounds such as 1-butylnaphthalene-4-propionate endoperoxide or 1-methylnaphthalene-4-propionate endoperoxide generate 1 O 2 under physiological conditions in the dark [48,49]. The potential application of such compounds to generate ozone for treatment of various diseases remains to be explored.…”

Section: Discussionmentioning

confidence: 99%

Alternatives to the ‘water oxidation pathway’ of biological ozone formation

Onyango

2015

J Chem Biol

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Recent studies have shown that ozone (O 3 ) is endogenously generated in living tissues, where it makes both positive and negative physiological contributions. A pathway for the formation of both O 3 and hydrogen peroxide (H 2 O 2 ) was previously proposed, beginning with the antibody or amino acid-catalyzed oxidation of water by singlet oxygen ( This article highlights key literature indicating that the oxidation of organic molecules such as the amino acids methionine, tryptophan, histidine, and cysteine by 1 O 2 is involved in ozone formation. Based on this, an alternative hypothesis for ozone formation is developed involving a further reaction of singlet oxygen with various oxidized organic intermediates. H 2 O 2 having water-derived oxygen atoms is subsequently formed during ozone decomposition in water by known reactions.

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“…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. 8) Secosterols have the ability to modify proteins covalently, including apolipoprotein CII, amyloid-peptide, -synuclein, and p53 accelerating amyloidogenesis and fibrilization.…”

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confidence: 99%

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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Formation of cholesterol ozonolysis products through an ozone-free mechanism mediated by the myeloperoxidase–H2O2–chloride system

Cited by 31 publications

References 20 publications

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

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

Alternatives to the ‘water oxidation pathway’ of biological ozone formation

Cytotoxic Effects of Secosterols and Their Derivatives on Several Cultured Cells

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