Generation of Cholesterol Carboxyaldehyde by the Reaction of Singlet Molecular Oxygen [O(2) ((1)Delta(g))] as Well as Ozone with Cholesterol
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
20/10/2012
20/10/2012
2009
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Resumo |
A few years ago, it was reported that ozone is produced in human atherosclerotic arteries, on the basis of the identification of 3 beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3 beta-hydroxy-5 beta-hydroxy-B-norcholestane-6 beta-carboxaldehyde (ChAld) as their 2,4-dinitrophenylhydrazones. The formation of endogenous ozone was attributed to water oxidation catalyzed by antibodies, with the formation of dihydrogen trioxide as a key intermediate. We now report that ChAld is also generated by the reaction of cholesterol with singlet molecular oxygen [O(2) ((1)Delta(g))] that is produced by photodynamic action or by the thermodecomposition of 1,4-dimethylnaphthalene endoperoxide, a defined pure chemical source of O(2) ((1)Delta(g)). On the basis of (18)O-labeled ChAld mass spectrometry, NMR, light emission measurements, and derivatization studies, we propose that the mechanism of ChAld generation involves the formation of the well-known cholesterol 5 alpha-hydroperoxide (5 alpha-OOH) (the major product of O(2) ((1)Delta(g))-oxidation of cholesterol) and/or a 1,2-dioxetane intermediate formed by O(2) ((1)Delta(g)) attack at the Delta(5) position. The Hock cleavage of 5 alpha-OOH (the major pathway) or unstable cholesterol dioxetane decomposition (a minor pathway, traces) gives a 5,6-secosterol intermediate, which undergoes intramolecular aldolization to yield ChAld. These results show clearly and unequivocally that ChAld is generated upon the reaction of cholesterol with O(2) ((1)Delta(g)) and raises questions about the role of ozone in biological processes. FAPESP (Fundacao de Amparo A Pesquisa do Estado de SAO Paulo) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) CNPq (Conselho Nacional para o Desenvolvimento Cientifico e Tecnologico) Instituto do Milenio: Redoxoma Instituto do Milenio: Redoxoma INCT de Processos Redox em Biomedicina-Redoxoma INCT de Processos Redox em Biomedicina-Redoxoma Fundo Bunka de Pesquisa - Banco Sumitomo Mitsui Fundo Bunka de Pesquisa - Banco Sumitomo Mitsui |
Identificador |
CHEMICAL RESEARCH IN TOXICOLOGY, v.22, n.5, p.875-884, 2009 0893-228X http://producao.usp.br/handle/BDPI/30839 10.1021/tx800447b |
Idioma(s) |
eng |
Publicador |
AMER CHEMICAL SOC |
Relação |
Chemical Research in Toxicology |
Direitos |
restrictedAccess Copyright AMER CHEMICAL SOC |
Palavras-Chave | #LINOLEIC-ACID HYDROPEROXIDE #OXIDATIVE RADICAL REACTIONS #LIPID-PEROXIDATION #BIOLOGICAL-SYSTEMS #PHOTOSENSITIZED OXIDATION #ALLYLIC HYDROPEROXIDES #ALZHEIMERS-DISEASE #CHEMI-LUMINESCENCE #STEROL METABOLISM #DNA-DAMAGE #Chemistry, Medicinal #Chemistry, Multidisciplinary #Toxicology |
Tipo |
article original article publishedVersion |