Review of progress in sterol oxidations: 1987–1995

Smith, Leland L.

doi:10.1007/bf02522641

Cited by 237 publications

(205 citation statements)

References 970 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%

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%

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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“…To confirm identification by GC, equipment can be coupled to a MS. Taking into account that HPLC greatly simplifies the quantification procedure and introduces fewer artifacts, normal phase (NP) and reversed-phase (RP) methods have been applied to the separation of oxysterols by several researchers Park & Addis, 1992;Smith, 1996). NP-liquid chromatography systems generally proved to be more effective than RP, but full resolution over the entire polarity range of oxidation products was not achieved .…”

Section: Oxysterolsmentioning

confidence: 99%

Cholesterol oxidation: Health hazard and the role of antioxidants in prevention

Valenzuela

Sanhueza²,

Nieto³

2003

Biol. Res.

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BIOLOGICAL IMPORTANCE OF CHOLESTEROLSterol cholesterol (cholest-5-en-ß-ol) is an essential metabolite required for major biological functions, such as the cell membrane structure where the steroid f o r m s , t o g e t h e r w i t h p h o s p h o l i p i d molecules, the integral part of the lipid b i l a y e r ( S p e c t o r & Y o r e k , 1 9 8 5 ) . Cholesterol is inserted into membrane bilayers with its long axis perpendicular to the plane of the membrane, preventing the crystallization of fatty acyl chains by fitting b e t w e e n t h e m ( Y e a g l e , 1 9 8 5 ) a n d modifying the activity of membranebounded enzymes (Valencia et al., 1999). Cholesterol also provides the structural scaffolding for the synthesis of steroids a n d s t e r o i d h o r m o n e s , a n d f o r t h e biosynthesis of bile and bile acid salts. Sterol plays also an important role in embryonic development (Roux et al., 2000). ABSTRACTCholesterol is a molecule with a double bond in its structure and is therefore susceptible to oxidation leading to the formation of oxysterols. These oxidation products are found in many commonly-consumed foods and are formed during their manufacture and/or processing. Concern about oxysterols consumption arises from the potential cytotoxic, mutagenic, atherogenic, and possibly carcinogenic effects of some oxysterols. Eggs and egg-derived products are the main dietary sources of oxysterols. Thermally-processed milk and milk-derived products are another source of oxysterols in our diet. Foods fried in vegetable/animal oil, such as meats and French-fried potatoes, are major sources of oxysterols in the Western diet. Efforts to prevent or to reduce cholesterol oxidation are directed to the use of antioxidants of either synthetic or natural origin. Antioxidants are not only able to inhibit triglyceride oxidation, some of them can also inhibit cholesterol oxidation. Among synthetic antioxidants 2,6-ditertiarybutyl-4-methylphenol (BHT), and tertiary butylhydroquinone (TBHQ) can efficiently inhibit the thermalinduced oxidation of cholesterol. Some natural antioxidants, such as alpha-and gamma-tocopherol, rosemary oleoresin extract, and the flavonoid quercetin, show strong inhibitory action against cholesterol oxidation.

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“…These activities have led to many studies of oxysterols, usually as toxins in the environment and foods (9,10), or as implicated in atherosclerosis (11)(12)(13)(14). The relatively greater sensitivity of certain malignant, as opposed to normal, cells offers an opportunity to use oxysterols as chemotherapeutic drugs.…”

mentioning

confidence: 99%

Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells

Johnson

Russell

Крылов

et al. 2000

Lipids

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Three oxidized analogs of cholesterol have been characterized for their ability to cause apoptotic cell death in CEM-C7-14 human leukemic cells. In addition to testing 15-ketocholestenol (K15), 15-ketocholestenol hydroxyethyl ether (CK15), and 7-ketocholesterol hydroxyethyl ether (CK7), an oxysterol of known apoptotic response, 25-hydroxycholesterol (25OHC), served as a standard for comparison. Growth studies based on dye exclusion by viable cells while using a sublethal concentration of oxysterols ranked their potency for cell kill as 25OHC > K15 > CK15 > CK7. Both the TUNEL assay (terminal deoxynucleotidyl transferase-mediated dUTP-X nick end labeling), which quantifies the amount of DNA nicks caused by a toxic agent, and the MTT assay, which measures cell metabolism and thus reflects cell viability, substantiated the same rank order. An ELISA assay for evaluating release of DNA fragments into the cytosol after treatment gave a similar potency order. The oncogene c-myc mRNA was suppressed by all three oxysterols, with 25OHC and K15 being the most potent suppressors. Hoechst and Annexin V staining documented that these oxysterols kill cells by an apoptotic pathway as evidenced by condensation of nuclear chromatin and plasma membrane inversion, respectively. From these in vitro studies, we believe that 25OHC, K15, and possibly CK15 have the potential to be chemotherapeutic agents.Paper no. L8259 in Lipids 35, 305-315 (March 2000).Both glucocorticoids and oxysterols can cause apoptosis of certain cells. For this action, glucocorticoids require a specific cytosolic protein, the glucocorticoid receptor (GR). No oxysterol receptor has been unequivocally identified, although two cellular proteins do specifically bind oxysterols: the oxysterol binding protein (OBP) and LXR, a member of the nuclear receptor family of proteins. As yet it is not certain that either protein is required for oxysterols' apoptotic actions. In our test system, the human leukemic cell line CEM, analysis of the events following addition of either class of steroid shows similarities at several points. These include a delay of about 1 d before the activation of caspases and nucleases, which occurs around the time of overt apoptosis. During this initial phase of cell death when the steroidal effects can be reversed, both types of steroids cause profound suppression of the oncogene product, cMyc (1,2). Because of their apoptotic action, glucocorticoids are used widely as antileukemic drugs. The similarity of effects of oxysterols suggests that they also might have therapeutic usefulness, alone, or in conjunction with glucocorticoids. Oxysterols are able to elicit changes in cholesterol synthesis, cell growth, and membrane composition, and can cause immunosuppression (3-8). These activities have led to many studies of oxysterols, usually as toxins in the environment and foods (9,10), or as implicated in atherosclerosis (11-14). The relatively greater sensitivity of certain malignant, as opposed to normal, cells offers an opportunity to use...

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Review of progress in sterol oxidations: 1987–1995

Abstract: Material dealing with the chemistry, biochemistry, and biological activities of oxysterols is reviewed for the period 1987-1995. Particular attention is paid to the presence of oxysterols in tissues and foods and to their physiological relevance.

Cited by 237 publications

References 970 publications

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

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

Cholesterol oxidation: Health hazard and the role of antioxidants in prevention

Structure‐apoptotic potency evaluations of novel sterols using human leukemic cells

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