Preparative singlet oxygenation of linoleate provides doubly allylic dihydroperoxides: Putative intermediates in the generation of biologically active aldehydes in vivo
ABSTRACT Photoinduced oxygenation generates biologically active, oxidatively truncated lipids in the retina. Previously, doubly allylic dihydroperoxides, 9,12-dihydroperoxyoctadeca-10,13-dienoic acid (9,12-diHPODE) and 10,13-dihydroperoxyoctadeca-8,11-dienoic acid (10,13-diHPODE), were postulated as key intermediates in the free radical-promoted oxidative fragmentation of linoleate that generates aldehydes, such as the cytotoxic gamma-hydroxyalkenal 4-hydroxy-2-nonenal (HNE), in vivo. We now report an efficient preparation of regioisomerically pure 9,12- and 10,13-diHPODE, devised to enable studies of their fragmentation reactions. Free radical-induced oxygenation of linoleate initially generates conjugated monohydroperoxy octadecadienoates (HPODEs) that are then converted into diHPODEs. In contrast, we found that singlet oxygenation of conjugated HPODEs does not produce diHPODEs. Unconjugated HPODEs are unique products of singlet oxygenation of linoleate that are coproduced with conjugated HPODEs. Preparative separation of the mixture of regioisomeric mono and diHPODEs generated by singlet oxygenation of linloeate is impractical. However, a simple tactic circumvented the problem. Thus, selective conversion of the undesired conjugated HPODEs into Diels-Alder adducts could be accomplished under mild conditions by reaction with N-phenyltriazolinedione. These adducts were readily removed, and the two remaining unconjugated HPODEs could then be easily isolated regioisomerically pure. Each of these was subsequently converted into a different, regioisomerically pure, diHPODE through further singlet oxygenation.
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- "However, Pryor et al.  have proposed a mechanism by which hydroperoxides of a diene system (e.g., linoleic acid) may produce such bicyclic endoperoxides. Zhang et al.  reported the production of doubly allylic dihydroperoxide from linoleic acid using singlet oxygen. This suggests that LOP may contain γ-ketoaldehydes with reactivity and behavior similar to those of isoLG's. "
ABSTRACT: Macrophages are prominent components of human atherosclerotic lesions and they are believed to accelerate the progression and/or complications of both early and advanced atherosclerotic lesions. We and others have shown that oxidized low-density lipoprotein (oxLDL) induces growth and inhibits apoptosis in murine bone marrow-derived macrophages. In this study, we sought to characterize the oxidative modification of LDL that is responsible for this prosurvival effect. We found that both the modified lipid and the modified protein components of oxLDL can increase the viability of macrophages. The key modification appeared to involve derivatization of amino groups in apoB or in phosphatidylethanolamine by lipid peroxidation products. These reactive oxidation products were primarily unfragmented hydroperoxide- or endoperoxide-containing oxidation products of linoleic acid or arachidonic acid. LC-MS/MS studies showed that some of the arachidonic acid-derived lysine adducts were isolevuglandins that contain lactam and hydroxylactam rings. MS/MS analysis of linoleic acid autoxidation adducts was consistent with 5- or 6-membered nitrogen-containing heterocycles derived from unfragmented oxidation products. The amine modification by oxidation products generated a fluorescence pattern with an excitation maximum at 350nm and emission maximum at 430nm. This is very similar to the fluorescence spectrum of copper-oxidized LDL.Free Radical Biology and Medicine 09/2011; 51(10):1926-36. DOI:10.1016/j.freeradbiomed.2011.08.029 · 5.71 Impact Factor
Conference Paper: Comparing color edge detection and segmentation methods[Show abstract] [Hide abstract]
ABSTRACT: The authors report the results of a controlled comparative study of four proposed methods for extracting boundaries in static images using color information. The first two techniques are, more properly speaking, edge-detection methods. These include the adaptation of the Hueckel operator to color images by R. Nevatia (1977) and the DOOG (difference of offset Gaussians) operator proposed by R. Young (1985, 1986). The latter two methods are examples of region-based segmentation. These include the adaptation of R. Ohlander et al. (1978), region splitting by Y. Ohta et al. (1980), and the fuzzy c-means segmentation and edge-detection methods of T.L. Huntsberger et al. (1985). The methods are compared using both simulated, controlled images as well as a variety of natural scene images. Images with various levels of randomly additive noise provide some indication of the degradation of performance of these methods under noisy conditionsSoutheastcon '89. Proceedings. Energy and Information Technologies in the Southeast., IEEE; 05/1989
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ABSTRACT: Although investigation of the toxicological and physiological actions of alpha/beta-unsaturated 4-hydroxyalkenals has made great progress over the last 2 decades, understanding of the chemical mechanism of formation of 4-hydroxynonenal and related aldehydes has advanced much less. The aim of this review is to discuss mechanistic evidence for these non-enzymatic routes, especially of the underappreciated intermolecular pathways that involve dimerized and oligomerized fatty acid derivatives as key intermediates. These cross-molecular reactions of fatty acid peroxyls have also important implications for understanding of the basic initiation and propagation steps during lipid peroxidation and the nature of the products that arise.Journal of Biological Chemistry 07/2008; 283(23):15539-43. DOI:10.1074/jbc.R800001200 · 4.57 Impact Factor