Ozonation of cholesterol in the presence of ethanol: Identification of a cytotoxic ethoxyhydroperoxide molecule

Tagiri-Endo, Misako; Nakagawa, Kiyotaka; Sugawara, Tatsuya; Ono, Kaori; Miyazawa, Teruo

doi:10.1007/s11745-004-1228-0

Cited by 7 publications

(9 citation statements)

References 26 publications

(34 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A small portion (1 ml) of the ethanolic sample solution was subjected to LC-CL with on-line MS (LC-CL-MS) (22) to monitor the yield of SQ-OOH. For LC-CL-MS, an ODS column (CAPCELLPAK C18, 4.6 3 250 mm; Shiseido, Tokyo, Japan) was used with methanol at a flow rate of 1 ml/min.…”

Section: Preparation Of Standard Sq-ooh Isomersmentioning

confidence: 99%

Ion-trap tandem mass spectrometric analysis of squalene monohydroperoxide isomers in sunlight-exposed human skin

Nakagawa

Ibusuki

Suzuki

et al. 2007

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

We previously discovered that squalene monohydroperoxide (SQ-OOH) was produced on human forehead skin and suggested that skin squalene (SQ) may be the principal target lipid for oxidative stress (e.g., sunlight exposure). Because of its six double bonds, SQ peroxidation can yield various positional hydroperoxide isomers. However, the structural characterization of skin SQ-OOH isomers has never been reported. Here, we prepared pure SQ-OOH isomers and developed an analytical method for SQ-OOH isomers using a quadrupole/linear ion-trap mass spectrometer (QTRAP) MS/MS system. Collision-induced dissociation produced specific fragment ions for each SQ-OOH isomer, which permitted discrimination between SQ-OOH isomers by multiple reaction monitoring (MRM). When lipid extract from human forehead skin was subjected to LC-MS/ MS with MRM, individual SQ-OOH isomers could be separated and detected with a sensitivity of 0.05 ng/injection. The total concentration of SQ-OOH isomers in forehead skin was ?956 mg/g skin lipids, but it increased up to 2,760 mg/g skin lipids after 3 h of sunlight exposure. The LC-MS/MS method was useful for investigating the peroxidation mechanisms of SQ as well as SQ-OOH-mediated skin disorders.-

show abstract

Section: Preparation Of Standard Sq-ooh Isomersmentioning

confidence: 99%

Ion-trap tandem mass spectrometric analysis of squalene monohydroperoxide isomers in sunlight-exposed human skin

Nakagawa

Ibusuki

Suzuki

et al. 2007

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Alternatively, the vinyl hydroperoxide may be generated for product III [26,30]. In addition, what we assume to be hydroxyhydroperoxide (HHP), methoxyhydroperoxide (MHP) products are observed at m/z 531 and 545, respectively [29,31]. The proposed structures of products and reaction mechanisms are shown in Scheme 2.…”

Section: Air-liquid Interfacial Reaction Of Cholso 4 With Omentioning

confidence: 99%

“…The products at m/z 481, 497, and 513 correspond to singly (+16), doubly (+32), and triply (+48) oxygenated CholSO 4 , respectively. Based on the previous studies of ozonolysis of Chol [25][26][27][28][29], singly, doubly, and triply oxygenated products are suggested as epoxide (product I, m/z 481), dicarbonyl (product II, m/z 497), and carbonyl-acid (product III, m/z 513), respectively. Alternatively, the vinyl hydroperoxide may be generated for product III [26,30].…”

Section: Air-liquid Interfacial Reaction Of Cholso 4 With Omentioning

confidence: 99%

“…R is H for water and CH 3 for methanol. Proposed structures of products I, II, and III are adopted from Reference [25][26][27][28][29]. Proposed structures of products IV and V are adopted from Reference [29,31] aerosol reported bound multimeric products, which are formed through aggregated gas phase clusters [26].…”

Section: Air-liquid Interfacial Reaction Of Cholso 4 With Omentioning

confidence: 99%

See 1 more Smart Citation

Studying Interfacial Reactions of Cholesterol Sulfate in an Unsaturated Phosphatidylglycerol Layer with Ozone Using Field Induced Droplet Ionization Mass Spectrometry

Choi

Rhee

et al. 2011

J. Am. Soc. Mass Spectrom.

View full text Add to dashboard Cite

Field-induced droplet ionization (FIDI) is a recently developed ionization technique that can transferions from the surface of microliter droplets to the gas phase intact. The air-liquid interfacial reactions of cholesterol sulfate (CholSO 4 ) in a 1-palmitoyl-2-oleoyl-sn-phosphatidylglycerol (POPG) surfactant layer with ozone (O 3 ) are investigated using field-induced droplet ionization mass spectrometry (FIDI-MS). Time-resolved studies of interfacial ozonolysis of CholSO 4 reveal that water plays an important role in forming oxygenated products. An epoxide derivative is observed as a major product of CholSO 4 oxidation in the FIDI-MS spectrum after exposure of the droplet to O 3 for 5 s. The abundance of the epoxide product then decreases with continued O 3 exposure as the finite number of water molecules at the air-liquid interface becomes exhausted. Competitive oxidation of CholSO 4 and POPG is observed when they are present together in a lipid surfactant layer at the air-liquid interface. Competitive reactions of CholSO 4 and POPG with O 3 suggest that CholSO 4 is present with POPG as a well-mixed interfacial layer. Compared with CholSO 4 and POPG alone, the overall ozonolysis rates of both CholSO 4 and POPG are reduced in a mixed layer, suggesting the double bonds of both molecules are shielded by additional hydrocarbons from one another. Molecular dynamics simulations of a monolayer comprising POPG and CholSO 4 correlate well with experimental observations and provide a detailed picture of the interactions between CholSO 4 , lipids, and water molecules in the interfacial region.

show abstract

“…A portion (1 ml) of the dichloromethane sample was subjected to LC combined with UV, chemiluminescence (CL), and mass spectrometry (MS) (LC-UV/CL/MS) (22,23) to evaluate LOOH formation, as described below.…”

Section: Preparation Of Lipid Hydroperoxide References 2669mentioning

confidence: 99%

Preparation of pure lipid hydroperoxides

Ibusuki

Nakagawa

Asai

et al. 2008

Journal of Lipid Research

Self Cite

View full text Add to dashboard Cite

Increasing evidence of lipid peroxidation in food deterioration and pathophysiology of diseases have revealed the need for a pure lipid hydroperoxide (LOOH) reference as an authentic standard for quantification and as a compound for biological studies in this field. Generally, LOOH is prepared from photo-or enzymatically oxidized lipids; however, separating LOOH from other oxidation products and preparing pure LOOH is difficult. Early studies showed the usability of reaction between hydroperoxide and vinyl ether for preparation of pure LOOH. Because the reactivity of vinyl ether with LOOHs other than fatty acid hydroperoxides has never been reported, here, we employed the reaction for preparation of a wide variety of pure LOOHs. Phospholipid, cholesteryl ester, triacylglycerol, or fatty acid was photo-or enzymatically oxidized; the resultant crude sample containing hydroperoxide was allowed to react with a vinyl ether [2-methoxypropene (MxP)]. Liquid chromatography (LC) and mass spectrometry confirmed that MxP selectively reacts with LOOH, yielding a stable MxP adduct (perketal). The lipophilic perketal was eluted at a position away from that of intact LOOH and identified and isolated by LC. Upon treatment with acid, perketal released the original LOOH, which was finally purified by LC. Using our optimized purification procedures, for instance, we produced 75 mg of pure phosphatidylcholine hydroperoxide (.99%) from 100 mg of phosphatidylcholine. Our developed method expands the concept of the perketal method, which provides pure LOOH references. The LOOHs prepared by the perketal method would be used as "gold standards" in LOOH methodology. Because lipid peroxidation is involved in food deterioration (1) and pathophysiology of human diseases (2, 3), there has been a great interest in the accurate measurement of lipid hydroperoxide (LOOH) concentration. This can be performed by several quantitative methods (4-11), and the most sensitive and reliable one is chemiluminescence detection-liquid chromatography (CL-LC) (9-11). Since there is no approved LOOH calibrator ("gold standard") available, it is impossible to compare the LOOH levels from various laboratories around the world.Currently, researchers prepare their own in-house reference LOOH [i.e., lipids (e.g., phospholipids, cholesterols, triacylglycerols, and fatty acids)] are subjected to photo-(12), free radical (13), or enzymatic oxidation (14, 15). The resultant crude or partly purified LOOH is generally used as a calibrator. However, these references are neither officially approved nor do they correspond to each other, particularly with regard to their purity. As frequently mentioned by LOOH researchers, this problem is mainly caused by the difficulty in distinguishing and isolating LOOH from other oxidation products such as hydroxides (13). Therefore, efficient purification of a wide variety of LOOHs is the key to the development of the gold standard not only for the accurate quantification of LOOH but also for the evaluation of its biological fu...

show abstract

Ozonation of cholesterol in the presence of ethanol: Identification of a cytotoxic ethoxyhydroperoxide molecule

Cited by 7 publications

References 26 publications

Ion-trap tandem mass spectrometric analysis of squalene monohydroperoxide isomers in sunlight-exposed human skin

Ion-trap tandem mass spectrometric analysis of squalene monohydroperoxide isomers in sunlight-exposed human skin

Studying Interfacial Reactions of Cholesterol Sulfate in an Unsaturated Phosphatidylglycerol Layer with Ozone Using Field Induced Droplet Ionization Mass Spectrometry

Preparation of pure lipid hydroperoxides

Contact Info

Product

Resources

About