Sterol metabolism. XXV. Cholesterol oxidation by singlet molecular oxygen

Kulig, Martin J.; Smith, Leland L.

doi:10.1021/jo00960a050

Cited by 220 publications

(110 citation statements)

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“…Materials-Synthetic cholesterol derivatives were obtained from Steraloids, Inc. and Sigma Chemical Co. Cholesterol-5␣-hydroperoxide and 3␤-hydroxycholest-4-ene-6␣-hydroperoxide were synthesized by photooxidation of cholesterol (26). Antibodies were obtained from Santa Cruz Biotechnology and Upstate Biotechnology.…”

Section: Methodsmentioning

confidence: 99%

Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide

Nelson

Alkon

2005

Journal of Biological Chemistry

178

129

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Alzheimer's disease (AD) is characterized by accumulation of the neurotoxic peptide ␤-amyloid, which is produced by proteolysis of amyloid precursor protein (APP). APP is a large membrane-bound copper-binding protein that is essential in maintaining synaptic function and may play a role in synaptogenesis. ␤-Amyloid has been shown to contribute to the oxidative stress that accompanies AD. Later stages of AD are characterized by neuronal apoptosis. However, the biochemical function of APP and the mechanism of the toxicity of ␤-amyloid are still unclear. In this study, we show that both ␤-amyloid and APP can oxidize cholesterol to form 7␤-hydroxycholesterol, a proapoptotic oxysterol that was neurotoxic at nanomolar concentrations. 7␤-Hydroxycholesterol inhibited secretion of soluble APP from cultured rat hippocampal H19 -7/IGF-IR neuronal cells and inhibited tumor necrosis factor-␣-converting enzyme ␣-secretase activity but had no effect on ␤-site APPcleaving enzyme 1 activity. 7␤-Hydroxycholesterol was also a potent inhibitor of ␣-protein kinase C, with a K i of ϳ0.2 nM. The rate of reaction between cholesterol and ␤-amyloid was comparable to the rates of cholesterolmetabolizing enzymes (k cat ‫؍‬ 0.211 min ؊1 ). The rate of production of 7␤-hydroxycholesterol by APP was ϳ200 times lower than by ␤-amyloid. Oxidation of cholesterol was accompanied by stoichiometric production of hydrogen peroxide and required divalent copper. The results suggest that a function of APP may be to produce low levels of 7-hydroxycholesterol. Higher levels produced by ␤-amyloid could contribute to the oxidative stress and cell loss observed in Alzheimer's disease.

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Section: Methodsmentioning

confidence: 99%

Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide

Nelson

Alkon

2005

Journal of Biological Chemistry

178

129

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“…Superoxide production was followed using a modification of the photochemical assay described by Giannopolitis and Ries (7) RESULTS AND DISCUSSION Analysis of oxidation products of cholesterol is one of the best ways of distinguishing '02 production from the production of radical oxidizers such as 02 -. The reaction of '02 with cholesterol results primarily in the production of the Sa-hydroperoxide of cholesterol (10). Radical oxidations, such as those by O2--, produce many different products (primarily the 7a-and 7,Bhydroperoxides), but have never been shown to produce the 5a-hydroperoxide (19).…”

mentioning

confidence: 99%

Light-Induced Production of Singlet Oxygen and Superoxide by the Fungal Toxin, Cercosporin

Daub¹,

Hangarter²

1983

Plant Physiol.

148

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Cercosporin, a toxin produced by members of the fungal genus Cercospora, is a photosensitizing compound which rapidly kills plant cells in the light. We have found that cercosporin, when activated by light in the presence ofoxygen, is able to generate both singlet oxygen and superoxide ions. Cercosporin, when illuminated in the presence of 02, reacted with cholesterol to form the Sa-hydroperoxide of cholesterol which is only produced by reaction with singlet oxygen. Cercosporin, in the presence of light, 02, and a reducing substrate, was also able to reduce p-nitro blue tetrazolium chloride, a compound readily reduced by superoxide. Superoxide dismutase, a scavenger of superoxide, inhibited this reaction. Production of both singlet oxygen and superoxide by cercosporin must be considered when studying the possible mechanisms of resistance to cercosporin.

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“…Several reported steroidal allylic oxidation reactions have not been included in the tables due to low yields of 7-keto product, such as oxygen irradiation with and without photosensitizer [24] and Gif chemistry [25].…”

Section: Reported Methodsmentioning

confidence: 99%

“…In auto-oxidation, a peroxide is formed via singlet oxygen (ene reaction) at the C5 carbon [24], which rearranges to the C7 position [40,41]. Likewise, TBHP degradation by metal leads to radicals that form a C7 peroxide.…”

Section: Reported Methodsmentioning

confidence: 99%

A Short Review of Methods for the Allylic Oxidation of Δ5 Steroidal Compounds to Enones

Sg¹,

Jp²

2016

J Steroids Horm Sci

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Introduction of α, β-unsaturated ketones to ∆ 5 steroidal olefins changes the characteristics and biological function of those compounds. Several synthetic methods have been reported to accomplish carbonyl introduction to ∆ 5 steroidal olefins. Herein, this short review will catalogue many of those oxidative methods, particularly those proceeding through a peroxide intermediate and/or use chromium complexes as reagents. to undesired side products, one in particular being C25 for steroids with side chains [15]. Furthermore, cleavage of the side chain can occur concurrent with allylic oxidation [16].Protecting the C3 hydroxy group is commonly accomplish by esterification using acetic anhydride to make cholesteryl acetate. The authors of this review prefer esterification with benzoyl chloride since cholesteryl benzoate products can be more easily isolated with recrystallization in acetone and water than the steroidal acetates. This esterification is necessary because many oxidants and catalysts will convert the C3 hydroxyl group to a ketone [17].Due to interest in "green" or environmentally benign chemistry, chemists have questioned the ethics of earlier catalysts. Environmental and health concerns have motivated the search for new oxidants and catalysts [18]. From chromium based catalysts, the next phase in steroidal allylic oxidation manifested through more environmentally friendly metallic catalysts that use TBHP as an oxygen donor. Meanwhile, several methods have been reported to give steroidal oxidation without any metal catalysts using as sodium chlorite and sodium hypochlorite [19,20]. Additionally, recoverable heterogeneous catalysts, clay

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Sterol metabolism. XXV. Cholesterol oxidation by singlet molecular oxygen

Cited by 220 publications

References 0 publications

Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide

Oxidation of Cholesterol by Amyloid Precursor Protein and β-Amyloid Peptide

Light-Induced Production of Singlet Oxygen and Superoxide by the Fungal Toxin, Cercosporin

A Short Review of Methods for the Allylic Oxidation of Δ5 Steroidal Compounds to Enones

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