Oxygenation of biological membranes by the pure reticulocyte lipoxygenase.

Kühn, Hartmut; Belkner, J; Wiesner, Rainer; Brash, Alan R.

doi:10.1016/s0021-9258(17)44759-4

Cited by 231 publications

(39 citation statements)

References 36 publications

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“…Similar observations were made when esterified unsaturated fatty acids in biomembranes and lipoproteins were treated with rabbit reticulocyte lipoxygenase (18,46). The oxygenation products of esterified unsaturated fatty acids were reported to be less stereospecific and regiospecific than those of free fatty acids, and this tendency was prominent when the concentration of substrate was high (18,46). Consistent with these previous studies, our results showed that the PAF-like products from linoleate-containing PC induced by soybean and reticulocyte lipoxygenases under hypoxic conditions were also less regiospecific.…”

Section: Discussionsupporting

confidence: 64%

“…Previously, soybean lipoxygenase was reported to produce almost equal amounts of 13-and 9-hydroperoxides of linoleic acid at low oxygen concentrations (38). Similar observations were made when esterified unsaturated fatty acids in biomembranes and lipoproteins were treated with rabbit reticulocyte lipoxygenase (18,46). The oxygenation products of esterified unsaturated fatty acids were reported to be less stereospecific and regiospecific than those of free fatty acids, and this tendency was prominent when the concentration of substrate was high (18,46).…”

Section: Discussionsupporting

confidence: 59%

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Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase

Tokumura

Sumida

Toujima

et al. 2000

Journal of Lipid Research

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Phosphatidylcholines (PCs) with platelet-activating factor (PAF)-like biological activities are known to be generated by fragmentation of the sn -2-esterified polyunsaturated fatty acyl group. The reaction is free radical-mediated and triggered by oxidants such as metal ions, oxyhemoglobin, and organic hydroperoxides. In this study, we characterized the PAF-like phospholipids produced on reaction of PC having a linoleate group with lipoxygenase enzymes at low oxygen concentrations. When the oxidized PCs were analyzed by gas chromatography-mass spectrometry, two types of oxidatively fragmented PC were detected. One PC had an sn -2-short chain saturated or unsaturated acyl group (C 8 -C 13 ) with an aldehydic terminal; the abundant species were PCs with C 9 and C 13 . The other PC had a short chain saturated acyl group (C 6 -C 9 ) with a methyl terminal, and the most predominant species was PC with C 8 . When the extracts of oxidation products were subjected to catalytic hydrogenation, PCs having saturated acyl groups (C 6 -C 14 ) were detected; the most abundant was C 12 species. The less regiospecific formation of PAF-like lipids suggests that they were generated by oxidative fragmentation of PC hydroperoxides formed by non-stereoselective oxygenation of the alkyl radical of esterified linoleate that escaped from the active centers of lipoxygenases. One of the PAF-like PC with an aldehydic terminal was found to be bioactive; it inhibited the production of nitric oxide induced by lipopolysaccharide and interferon-␥ in vascular smooth muscle cells from rat aorta. -Tokumura, A

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Section: Discussionsupporting

confidence: 64%

Section: Discussionsupporting

confidence: 59%

Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase

Tokumura

Sumida

Toujima

et al. 2000

Journal of Lipid Research

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“…Cellular phospholipids containing oxidized forms of AA or linoleic acid could be originated in two ways: (i) direct oxidation of the fatty acid substituents at the sn-1 or sn-2 positions of glycerophospholipids and diacylglycerol and (ii) re-esteri®cation of oxidized acids with lysoglycero-phospholipids. Enzymatic oxidation of polyunsaturated lipids within glycerophosphatide substrates has been demonstrated under certain conditions, particularly in cell-free systems using exogenously supplied 15-LO (Brash et al, 1987;Ku Èhn et al, 1990). Consistently, all compounds tested were esteri®ed in vitro into phospholipids when epidermal cells were incubated with labeled compounds.…”

Section: Discussionmentioning

confidence: 67%

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Antón

Camacho

Puig

et al. 2002

Journal of Investigative Dermatology

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In previous studies we observed that normal human epidermis forms 12-oxo-eicosatetraenoic acid (12-oxo-ETE) and hepoxilin B3 (HxB3) as major eicosanoids, both being elevated in psoriasis. We also observed that normal epidermis, in a reaction probably catalyzed by 12-lipoxygenase, only synthesize one of the two possible 10-hydroxy epimers of HxB3. We have now extended these previous studies investigating further transformation of HxB3 into trioxilin B3 (TrXB3) and esterification of both into phospholipids. Phospholipids were extracted from normal epidermis and from psoriatic scales. A combination of high performance liquid chromatography and gas chromatography-mass spectrometry analysis demonstrated the occurrence of HxB3 and TrXB3 in the phospholipids of psoriatic lesions. Alkaline- and phospholipase-A2-mediated hydrolysis of the phospholipids yielded similar quantities of both HxB3 and TrXB3 indicating their preference for the sn-2 position of glycerophospholipids. The thin layer chromatography analysis of the phospholipid classes after incubation of epidermal cells with [14C]-labeled HxB3, TrXB3, 12-hydroxy-eicosatetraenoic acid (12-HETE), 12-oxo-ETE, or 15-HETE showed that 12-HETE was the most esterified (12-HETE >15-HETE > TrXB3 > 12-oxo-ETE > HxB3). HxB3 and TrXB3 were mainly esterified in phosphatidyl-choline and phosphatidyl-ethanolamine. HxB3 was also enzymatically converted into TrXB3 in vitro. HxB3 epoxide hydrolase-like activity was not observed when boiled tissue was incubated with [14C]-HxB3, this activity being located in the cytosol fraction (100,000 x g supernatant) of fresh tissue. These findings suggest that in vivo some part of HxB3 is transformed into TrXB3 and both compounds are partially incorporated into the phospholipids.

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“…1 5-LOXs are involved in the biosynthesis of leukotrienes that constitute important mediators of anaphylactic and inflammatory diseases. 1 In contrast to 5-LOXs, which strongly prefer free arachidonic acid as substrate, mammalian 15-LOXs are capable of oxygenating not only free, but also esterified polyenoic fatty acids, [2][3][4] and even more complex lipid protein assemblies such as biomembranes 2,4,5 and lipoproteins. 6 The enzyme is constitutively expressed in reticulocytes of various species, 7,8 in airway epithelial cells, and in eosinophilic granulocytes.…”

mentioning

confidence: 99%

“…The enzyme is commonly referred to as cytosolic protein because it can be purified from the cytosol of various mammalian cells 7 and because there is no obvious membrane binding sequence in its primary structure. On the other hand, its capability of directly oxygenating biomembranes [2][3][4][5] and the recent finding that in more mature reticulocytes the 15-LOX was predominantly detected in the stroma fraction 25 suggested a maturation-dependent membrane association of the enzyme.…”

mentioning

confidence: 99%

Membrane Translocation of 15-Lipoxygenase in Hematopoietic Cells Is Calcium-Dependent and Activates the Oxygenase Activity of the Enzyme

Brinckmann

Schnurr

Heydeck

et al. 1998

Blood

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Mammalian 15-lipoxygenases, which have been implicated in the differentiation of hematopoietic cells are commonly regarded as cytosolic enzymes. Studying the interaction of the purified rabbit reticulocyte 15-lipoxygenase with various types of biomembranes, we found that the enzyme binds to biomembranes when calcium is present in the incubation mixture. Under these conditions, an oxidation of the membrane lipids was observed. The membrane binding was reversible and led to an increase in the fatty acid oxygenase activity of the enzyme. To find out whether such a membrane binding also occurs in vivo, we investigated the intracellular localization of the enzyme in stimulated and resting hematopoietic cells by immunoelectron microscopy, cell fractionation studies and activity assays. In rabbit reticulocytes, the 15-lipoxygenase was localized in the cytosol, but also bound to intracellular membranes. This membrane binding was also reversible and the detection of specific lipoxygenase products in the membrane lipids indicated the in vivo activity of the enzyme on endogenous substrates. Immunoelectron microscopy showed that in interleukin-4 –treated monocytes, the 15-lipoxygenase was localized in the cytosol, but also at the inner side of the plasma membrane and at the cytosolic side of intracellular vesicles. Here again, cell fractionation studies confirmed the in vivo membrane binding of the enzyme. In human eosinophils, which constitutively express the 15-lipoxygenase, the membrane bound share of the enzyme was augmented when the cells were stimulated with calcium ionophore. Only under these conditions, specific lipoxygenase products were detected in the membrane lipids. These data suggest that in hematopoietic cells the cytosolic 15-lipoxygenase translocates reversibly to the cellular membranes. This translocation, which increases the fatty acid oxygenase activity of the enzyme, is calcium-dependent, but may not require a special docking protein.

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Oxygenation of biological membranes by the pure reticulocyte lipoxygenase.

Cited by 231 publications

References 36 publications

Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase

Structural identification of phosphatidylcholines having an oxidatively shortened linoleate residue generated through its oxygenation with soybean or rabbit reticulocyte lipoxygenase

Hepoxilin B3 and its Enzymatically Formed Derivative Trioxilin B3 are Incorporated into Phospholipids in Psoriatic Lesions

Membrane Translocation of 15-Lipoxygenase in Hematopoietic Cells Is Calcium-Dependent and Activates the Oxygenase Activity of the Enzyme

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