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1.
The relationship between changes in the cell wall, lipid peroxidation, proliferation, senescence and cell death 总被引:1,自引:0,他引:1
Gerhard Spiteller 《Physiologia plantarum》2003,119(1):5-18
Plants and mammals contain polyunsaturated fatty acids (PUFAs) in their membranes. PUFAs belong to the most oxygen sensitive molecules encountered in nature. It would seem that nature has selected this property of PUFAs for signalling purposes: PUFAs are stored in the surface of cells and organelles not in free form but conjugated to phospho‐ and galactolipids. Any change in membrane structure apparently activates membrane‐bound phospholipases, which cleave the conjugates. The obtained free PUFAs are substrates for lipoxygenases (LOX). These transform PUFAs to lipidhydroperoxides (LOOHs). LOOHs are converted to a great variety of secondary products. These lipid‐peroxidation (LPO) products and the resulting generated products thereof represent biological signals, which do not require a preceding activation of genes. They are produced as a non‐specific response to a large variety of external or internal impacts, which therefore do not need interaction with specific receptors. When, due to an external impact, e.g. attack of a microorganism, or to a change in temperature, the amount of liberated free PUFAs exceeds a certain threshold, LOX commit suicide. Thus iron ions, located in the active centre of LOX, are liberated. Iron ions react with LOOHs in the close surroundings by generating alkoxy radicals (LO.). These induce a non‐enzymatic LPO. A fraction of the LO. radicals generated from linoleic acid (LPO products derived from linoleic acid play a dominant role in signalling which was previously overlooked) is converted to 2,4‐dienals which induce the programmed cell death (PCD) and the hypersensitive reaction (HR). While peroxyl radicals (LOO.) generated as intermediates in the course of an enzymatic LPO are transformed within the enzyme complex to corresponding anions (LOO–), and thus lose their reactivity, peroxyl radicals generated in non‐enzymatic reactions are not deactivated. They not only react by abstraction of hydrogen atoms from activated X‐H bonds of molecules in their close vicinity, but also by epoxidation of double bonds and oxidation of a variety of biological molecules, causing a dramatic change in molecular structure which finally leads to cell death. As long as reducing agents, like glutathione, or compounds with free phenolic groups are available, the amount of LOOHs is kept low. Cell death is induced in a defined way by apoptosis. But when the reducing agents have been consumed, PCD seems to switch to necrotic processes. Thus proliferation is induced by minor changes at the cell membrane, while slow changes at cell membranes are linked with apoptosis (e.g. response to attack of microorganisms or drought) and necrosis (severe wounding), depending only on the amount, but not on the type, of applied stimulus. 相似文献
2.
Kanazawa A Sawa T Akaike T Morimur S Kida K Maeda H 《BioFactors (Oxford, England)》2000,13(1-4):187-193
Lipid hydroperoxides (LOOH or oxidized oils) are known as unfavorable food components. Molecular details of the fate and mechanisms of LOOH to exert adverse effects in vivo are, however, little understood. In the present study, we demonstrated that LOOH generated alkylperoxyl radical (LOO*) after reaction with various heme compounds such as myoglobin, cytochrome c, hemin, hematin, etc., but little formation of other radical species was noticed such as L* or LO*. It was also shown that LOO* thus formed exhibits cytotoxicity and caused DNA damages including strand breakage and abasic site formation. This highly toxic LOO* is effectively scavenged by hot water extracts of vegetable (soup), flavonoids, polyphenols as well as tocopherols. Another important finding is that crude vegetable oils are rich in potent-LOO* scavenging activity, which exhibits potent anti-oxidant activity as well; whereas highly purified oils are scanty in such components and LOO* scavenging activity. These findings imply that a considerate processing in the refining of oils should be needed to retain such potent endogenous anti-oxidative radical scavenging-components. 相似文献
3.
The Important Role of Lipid Peroxidation Processes in Aging and Age Dependent Diseases 总被引:1,自引:0,他引:1
Spiteller G 《Molecular biotechnology》2007,37(1):5-12
Any change in the cell membrane structure activates lipoxygenases (LOX). LOX transform polyunsaturated fatty acids (PUFAs)
to lipidhydroperoxide molecules (LOOHs). When cells are severely wounded, this physiological process switches to a non-enzymatic
lipid peroxidation (LPO) process producing LOO· radicals. These oxidize nearly all-biological molecules such as lipids, sugars, and proteins. The LOO· induced degradations proceed by transfer of the radicals from cell to cell like an infection. The chemical reactions induced
by LO· and LOO· radicals seem to be responsible for aging and induction of age dependent diseases.
Alternatively, LO· and LOO· radicals are generated by frying of fats and involve cholesterol-PUFA esters and thus induce atherogenesis.
Plants and algae are exposed to LOO· radicals generating radiation. In order to remove LOO· radicals, plants and algae transform PUFAs to furan fatty acids, which are incorporated after consumption of vegetables into
mammalian tissues where they act as excellent scavengers of LOO· and LO· radicals.
Figure 6 of this article is reprinted from the paper of G. Spiteller: “Peroxyl radicals: Inductors of neurodegenerative and
other inflammatory diseases. Their origin and how they transform cholesterol, phospholipids, plasmalogens, polyunsaturated
fatty acids, sugars and proteins into deleterious products” published in Free Radic. Biol. Med. 41, 362–387 (2006) Elsevier,
2006 by permission from Elsevier. 相似文献
4.
Lipid peroxidation (LPO) of polyunsaturated fatty acids (PUFAs) is suspected to be involved in the generation of chronic diseases. A model reaction for LPO is the air oxidation of PUFAs initiated by Fe2+ and ascorbic acid. In the course of such model reactions glycolaldehyde (GLA) was detected as main aldehydic product. Since it is difficult to explain the generation of GLA by oxidation of PUFAs, it was suspected that GLA might be derived by oxidation of ascorbic acid. This assumption was verified by treatment of ascorbic acid with Fe2+.
Produced aldehydic compounds were trapped by addition of pentafluorobenzylhydroxylamine hydrochloride (PFBHA-HCl), trimethylsilylated and finally identified by gas chromatography/mass spectrometry (GC/MS). Oxidation of ascorbic acid with O2 in presence of iron ions produced not only glycolaldehyde (GLA), but also glyceraldehyde (GA), dihydroxyacetone (DA) and formaldehyde. Glyoxal (GO) and malondialdehyde (MDA) were detected as trace compounds.
The yield of the aldehydic compounds was increased by addition of lipid hydroperoxides (LOOH) or H2O2. The buffer influenced the reaction considerably: Iron ions react with Tris buffer by producing dihydroxyace-tone (DA). Since ascorbic acid is present in biological systems and Fe2+ ions are obviously generated by cell damaging processes, the production of GLA and other aldehydic components might add to the damaging effects of LPO.
Glucose suffers also oxidation to short-chain aldehydic compounds in aqueous solution, but this reaction requires addition of equimolar amounts of Fe2+ together with equimolar amounts of H2O2 or 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-HPODE). Therefore this reaction, also influenced by the buffer system, seems to be not of biological relevance. 相似文献
Produced aldehydic compounds were trapped by addition of pentafluorobenzylhydroxylamine hydrochloride (PFBHA-HCl), trimethylsilylated and finally identified by gas chromatography/mass spectrometry (GC/MS). Oxidation of ascorbic acid with O2 in presence of iron ions produced not only glycolaldehyde (GLA), but also glyceraldehyde (GA), dihydroxyacetone (DA) and formaldehyde. Glyoxal (GO) and malondialdehyde (MDA) were detected as trace compounds.
The yield of the aldehydic compounds was increased by addition of lipid hydroperoxides (LOOH) or H2O2. The buffer influenced the reaction considerably: Iron ions react with Tris buffer by producing dihydroxyace-tone (DA). Since ascorbic acid is present in biological systems and Fe2+ ions are obviously generated by cell damaging processes, the production of GLA and other aldehydic components might add to the damaging effects of LPO.
Glucose suffers also oxidation to short-chain aldehydic compounds in aqueous solution, but this reaction requires addition of equimolar amounts of Fe2+ together with equimolar amounts of H2O2 or 13-hydroperoxy-9-cis-11-trans-octadecadienoic acid (13-HPODE). Therefore this reaction, also influenced by the buffer system, seems to be not of biological relevance. 相似文献
5.
Oxylipins derived mainly from C20- and C22-polyunsaturated fatty acids (PUFAs), termed lipid mediators (LMs), are essential signalling messengers involved in human physiological responses associated with homeostasis and healing process for infection and inflammation. Some LMs involved in the resolution of inflammation and infection are termed specialized pro-resolving mediators (SPMs), which are generated by human M2 macrophages or polymorphonuclear leukocytes and have the potential to protect and treat hosts from bacterial and viral infections by phagocytosis activation. Lipoxygenases (LOXs) biosynthesize regio- and stereoselective LMs. Thus, understanding the regio- and stereoselectivities of LOXs for PUFAs at a molecular level is important for the biocatalytic synthesis of diverse LMs. Here, we elucidate the catalytic mechanisms and discuss regio- and stereoselectivities and their changes of LOXs determined by insertion direction and position of the substrate and oxygen at a molecular level for the biosynthesis of diverse human LMs. Recently, the biocatalytic synthesis of PUFAs to human LMs or analogues has been conducted using microbial LOXs. Such microbial LOXs involved in the biosynthesis of LMs are expected to exert significantly higher activity and stability than human LOXs. Diverse regio- and stereoselective LOXs can be obtained from microorganisms, which represent a wealth of genomic sources. We reconstruct the biosynthetic pathways of LOX-catalyzed LMs in humans and other organisms. Furthermore, we suggest the effective methods of biocatalytic synthesis of diverse human LMs from PUFAs or glucose by using microbial LOXs, increasing the stability and activity of LOXs, combining the reactions of LOXs, and constructing metabolic pathways. 相似文献
6.
It is demonstrated that the perhydroxyl radical (HOO., the conjugate acid of superoxide (O2-], initiates fatty acid peroxidation (a model for biological lipid peroxidation) by two parallel pathways: fatty acid hydroperoxide (LOOH)-independent and LOOH-dependent. Previous workers (Gebicki, J. M., and Bielski, B. H. J. (1981) J. Am. Chem. Soc. 103, 7020-7025) demonstrated that HOO., generated by pulse radiolysis, initiates peroxidation in ethanol/water fatty acid dispersions by abstraction of the bis-allylic hydrogen atom from a polyunsaturated fatty acid. Addition of O2 to the fatty acid radicals forms peroxyl radicals (LOO.s), the chain-propagating species of lipid peroxidation. In this work it is demonstrated that HOO., generated either chemically (KO2) or enzymatically (xanthine oxidase), is a good initiator of fatty acid peroxidation in linoleic acid ethanol/water dispersions; O2- serves only as the source of HOO., and HOO. initiation can be observed at physiologically relevant pH values. In contrast to the previous results, the initiating effectiveness of HOO. is related directly to the initial concentrations of LOOHs in the lipids to be peroxidized. This defines a LOOH-dependent mechanism for fatty acid peroxidation initiation by HOO., which parallels the previously established LOOH-independent pathway. Since the LOOH-dependent pathway is much more facile than the LOOH-independent pathway, LOOH is the kinetically preferred site of HOO. attack in these systems. Experiments comparing HOO./LOOH-dependent fatty acid peroxidation with transition metal- and peroxyl radical-initiated peroxidation rule out the participation of the latter two species as initiators, which defines the HOO./LOOH initiation system as mechanistically unique. LOOH product studies are consistent with either a direct or indirect hydrogen atom transfer between LOOH and HOO. to yield LOO.s, which propagate peroxidation. The LOOH-dependent pathway of HOO.-initiated fatty acid peroxidation may be relevant to mechanisms of lipid peroxidation initiation in vivo. 相似文献
7.
Reactions of linoleic acid peroxyl radicals with phenolic antioxidants: a pulse radiolysis study 总被引:1,自引:0,他引:1
M Erben-Russ W Bors M Saran 《International journal of radiation biology and related studies in physics, chemistry, and medicine》1987,52(3):393-412
Linoleic acid peroxyl radicals (LOO.) can be viewed as model intermediates occurring during lipid peroxidation processes. Formation and reactions of these species were investigated in aqueous alkaline solution using the technique of pulse radiolysis combined with kinetic spectroscopy. Irradiation of linoleic acid in N2O/O2-saturated solutions leads to a mixture of peroxyl radical isomers, whereas reaction of 13-hydroperoxylinoleic acid (13-LOOH) with azide radicals in N2O-saturated solution produces 13-LOO. radicals specifically. These peroxyl radicals cannot be observed directly, but their reactions with the two flavonols, kaempferol and quercetin, acting as radical-scavenging antioxidants, produced strongly absorbing aroxyl radicals (ArO.). The same aroxyl radicals were generated by .OH and N3. with rate constants exceeding 10(9) dm3 mol-1 s-1. Applying a reaction scheme that includes competing generation and decay reactions of both LOO. and ArO. radicals, we derived individual rate constants for LOO. reactions with the phenols (greater than 10(7) dm3 mol-1 s-1), with the aroxyl radicals to form covalent adducts (greater than 10(8) dm3 mol-1 s-1), as well as for their bimilecular decay (3.0 X 10(8) dm3 mol-1 s-1). These results demonstrate the high reactivity of both fatty acid peroxyl radicals and the flavone antioxidants in aqueous solution. 相似文献
8.
We have studied the effects of the interaction of radiation generated human serum albumin radicals (HSA*) with human hemoglobin molecules (Hb). Diluted Hb aqueous solutions were irradiated under N2O or argon without HSA and in the presence of HSA. Analysis of Hb absorbance spectra in the visible range, cross-linking of HSA* radicals with Hb molecules and functional properties of Hb were investigated. The degree of Hb destruction estimated on the basis of changes in the absorption spectra indicated that the effectiveness of HSA* radicals generated under N2O for Hb destruction was approximately equal to that of *OH radicals. In this case mainly *OH radicals formed the secondary HSA* radicals. However, during the irradiation Hb + HSA under argon the presence of equivalent amounts of oxidizing and reducing products of water radiolysis lowers the degree of Hb destruction. Some reactions of HSA* radicals with Hb molecules lead to the formation of covalent bonds between the molecules of both proteins. The following types of hybrids could be distinguished: Hb monomer-HSA, Hb dimer-HSA and higher aggregates. Structural changes of Hb by HSA* radicals were reflected by alterations in the oxygen affinity (increase) and cooperativity (decrease) of Hb. The results obtained indicate that in the experimental systems studied, the HSA* radical reactions with Hb molecules are favoured over recombination reactions of HSA* radicals. On this basis one can suggest that in the studied systems Hb plays the role of an acceptor of radical energy located on HSA. 相似文献
9.
The 21-aminosteroid inhibitors of lipid peroxidation: reactions with lipid peroxyl and phenoxy radicals 总被引:4,自引:0,他引:4
The 21-aminosteroids U74006F and U74500A have been examined for their ability to scavenge the lipid peroxyl (LOO.) and phenoxy (PhO.) radicals. Lipid peroxidation was followed by measuring the formation of linoleic acid hydroperoxide (LOOH; 18:200H) from linoleic acid during incubations in methanol at 37 degrees C. Initiation of lipid peroxidation was by the radical generator 2,2'-azobis(2,4-dimethylvaleronitrile; AMVN), which under the conditions employed, initiated LOOH formation at a constant rate of 22 microM/h with a kinetic chain length of 21. Alpha-tocopherol (alpha TC) nearly completely blocked the chain reaction by scavenging LOO., reducing its formation to that essentially attributable to initiation alone. The average inhibition rate constant kinh for alpha TC at 37 degrees C was calculated as 4.9 x 10(5) M-1 sec-1. U74006F or U74500A also inhibited LOOH formation, reducing its rate to a constant fraction of control in a concentration dependent manner. U74500A was a more potent scavenger of LOO. than U74006F; however, both compounds were considerably less potent than alpha TC based upon their respective kinh's at 37 degrees C. Similarly, alpha TC, U74006F and U74500A scavenged PhO.. As seen with LOO. scavenging, alpha TC was orders of magnitude more reactive toward PhO. than either 21-aminosteroid as judged by their respective second order rate constants (k2). Both U74006F and U74500A were degraded during their reaction with LOO. or PhO. to as yet uncharacterized product(s). The data indicate that while the 21-aminosteroids can scavenge lipid radicals, their activity in this regard is less than expected based upon their ability to inhibit iron dependent lipid peroxidation. 相似文献
10.
H Aoshima K Kadoya H Taniguchi T Satoh H Hatanaka 《Bioscience, biotechnology, and biochemistry》1999,63(6):1025-1031
The exposure of Saccharomyces cerevisiae cells to 13-L-hydroperoxylinoleic acid (LOOH) caused their death, the degree of which was dependent on the growth phase of the cells. Pre-application of ethanol, hydrogen peroxide (H2O2) and LOOH to S. cerevisiae cells reduced the effect of LOOH on the cells, showing the transient cross adaptation to LOOH. Antioxidants such as N,N',-diphenyl-p-phenylenediamine (DPPD), melatonin and vitamin E, and inhibitors of permeability transition of mitochondria, cyclosporin A and trifluoperazine, inhibited the LOOH-triggered cell death, while an inhibitor of glutathione synthetase, buthionine sulfoximine (BSO), enhanced the cell death by LOOH. Reactive oxygen species (ROS) were detected by flow cytometry, using the ROS-specific fluorescent indicator. A ferric iron chelator, deferoxamine, inhibited the LOOH-triggered cell death, and peroxyl radicals (LOO.) were detected by a spin trapping method. These reactive radicals possibly induced the death of S. cerevisiae cells. However, the DNA fragmentation characteristic of apoptosis was not observed in S. cerevisiae cells after exposure to LOOH, staurosporine, dexamethasone or etoposide, which have been reported to cause apoptosis in mammalian cells. 相似文献
11.
Miyamoto S Ronsein GE Prado FM Uemi M Corrêa TC Toma IN Bertolucci A Oliveira MC Motta FD Medeiros MH Mascio PD 《IUBMB life》2007,59(4-5):322-331
The decomposition of lipid hydroperoxides (LOOH) into peroxyl radicals is a potential source of singlet molecular oxygen ((1)O(2)) in biological systems. Recently, we have clearly demonstrated the generation of (1)O(2) in the reaction of lipid hydroperoxides with biologically important oxidants such as metal ions, peroxynitrite and hypochlorous acid. The approach used to unequivocally demonstrate the generation of (1)O(2) in these reactions was the use of an isotopic labeled hydroperoxide, the (18)O-labeled linoleic acid hydroperoxide, the detection of labeled compounds by HPLC coupled to tandem mass spectrometry (HPLC-MS/MS) and the direct spectroscopic detection and characterization of (1)O(2) light emission. Using this approach we have observed the formation of (18)O-labeled (1)O(2) by chemical trapping of (1)O(2) with anthracene derivatives and detection of the corresponding labeled endoperoxide by HPLC-MS/MS. The generation of (1)O(2) was also demonstrated by direct spectral characterization of (1)O(2) monomol light emission in the near-infrared region (lambda = 1270 nm). In summary, our studies demonstrated that LOOH can originate (1)O(2). The experimental evidences indicate that (1)O(2) is generated at a yield close to 10% by the Russell mechanism, where a linear tetraoxide intermediate is formed in the combination of two peroxyl radicals. In addition to LOOH, other biological hydroperoxides, including hydroperoxides formed in proteins and nucleic acids, may also participate in reactions leading to the generation (1)O(2). This hypothesis is currently being investigated in our laboratory. 相似文献
12.
Microsomal lipid peroxidation: the role of NADPH--cytochrome P450 reductase and cytochrome P450 总被引:3,自引:0,他引:3
A Sevanian K Nordenbrand E Kim L Ernster P Hochstein 《Free radical biology & medicine》1990,8(2):145-152
The role of NADPH--cytochrome P450 reductase and cytochrome P450 in NADPH- and ADP--Fe3(+)-dependent lipid peroxidation was investigated by using the purified enzymes and liposomes prepared from either total rat-liver phospholipids or a mixture of bovine phosphatidyl choline and phosphatidyl ethanolamine (PC/PE liposomes). The results suggest that NADPH- and ADP--Fe3(+)-dependent lipid peroxidation involves both NADPH--cytochrome P450 reductase and cytochrome P450. Just as in the case of cytochrome P450-linked monooxygenations, the role of these enzymes in lipid peroxidation may be to provide two electrons for O2 reduction. The first electron is used for reduction of ADP--Fe3+ and subsequent addition of O2 to the perferryl radical (ADP--Fe3(+)-O2-), which then extracts an H atom from a polyunsaturated lipid (LH) giving rise to a free radical (LH.) that reacts with O2 yielding a peroxide free radical (LOO.). The second electron is then used to reduce LOO. to the lipid hydroperoxide (LOOH). In the latter capacity, reduced cytochrome P450 can be replaced by EDTA--Fe2+ or by the superoxide radical as generated through redox cycling of a quinone such as menadione. 相似文献
13.
We report that a lactoperoxidase (LPO) metabolite derived from nitrite (NO2-) catalyses one-electron oxidation of biological electron donors and antioxidants such as NADH, NADPH, cysteine, glutathione, ascorbate, and Trolox C. The radical products of the reaction have been detected and identified using either direct EPR or EPR combined with spin trapping. While LPO/H2O2 alone generated only minute amounts of radicals from these compounds, the yield of radicals increased sharply when nitrite was also present. In aerated buffer (pH 7) the nitrite-dependent oxidation of NAD(P)H by LPO/H2O2 produced superoxide radical, O2*-, which was detected as a DMPO/*O2H adduct. We propose that in the LPO/H2O2/NO2-/biological electron donor systems the nitrite functions as a catalyst because of its preferential oxidation by LPO to a strongly oxidizing metabolite, most likely a nitrogen dioxide radical *NO2, which then reacts with the biological substrates more efficiently than does LPO/H2O2 alone. Because both nitrite and peroxidase enzymes are ubiquitous our observations point at a possible mechanism through which nitrite might exert its biological and cytotoxic action in vivo, and identify some of the physiological targets which might be affected by the peroxidase/H2O2/nitrite systems. 相似文献
14.
The effect of 13-L-hydroperoxylinoleic acid (LOOH) on both Xenopus oocytes and neurotransmitter receptors synthesized in the oocytes was studied by electrophysiological and ion flux measurement. Addition of LOOH to the incubation mixture of the oocytes raised the membrane potential and decreased the membrane resistance of the oocytes. These effects of LOOH on the oocytes were reversed within a few hours by incubation with frog Ringer solution. Addition of LOOH also caused an increase of Li+ and 45Ca2+ uptake into the oocytes. However, production of alkoxy radicals by the addition of FeCl2 to the incubation mixture containing LOOH did not accelerate the damage to the oocytes by LOOH. So essential toxicity is caused possibly by an increase in the membrane permeability resulting from disturbance of the lipid bilayer arrangement, not from production of active alkoxy radicals during decomposition of LOOH. Nicotinic acetylcholine and gamma-aminobutyric acid receptors were synthesized in Xenopus oocytes by injecting mRNA prepared from Electrophorus electricus electroplax and rat brain. LOOH noncompetitively inhibited the function of these receptors and also increased the rate of desensitization of the receptors. 相似文献
15.
The H(2)O(2)-dependent reaction of lactoperoxidase (LPO) with sperm whale myoglobin (SwMb) or horse myoglobin (HoMb) produces LPO-Mb cross-linked species, in addition to LPO and SwMb homodimers. The HoMb products are a LPO(HoMb) dimer and LPO(HoMb)(2) trimer. Dityrosine cross-links are shown by their fluorescence to be present in the oligomeric products. Addition of H(2)O(2) to myoglobin (Mb), followed by catalase to quench excess H(2)O(2) before the addition of LPO, still yields LPO cross-linked products. LPO oligomerization therefore requires radical transfer from Mb to LPO. In contrast to native LPO, recombinant LPO undergoes little self-dimerization in the absence of Mb but occurs normally in its presence. Simultaneous addition of 3,5-dibromo-4-nitrosobenzenesulfonic acid (DBNBS) and LPO to activated Mb produces a spin-trapped radical electron paramagnetic resonance signal located primarily on LPO, confirming the radical transfer. Mutation of Tyr-103 or Tyr-151 in SwMb decreased cross-linking with LPO, but mutation of Tyr-146, Trp-7, or Trp-14 did not. However, because DBNBS-trapped LPO radicals were observed with all the mutants, DBNBS traps LPO radicals other than those involved in protein oligomerization. The results clearly establish that radical transfer occurs from Mb to LPO and suggest that intermolecularly transferred radicals may reside on residues other than those that are generated by intramolecular reactions. 相似文献
16.
ω-6和ω-3类多不饱和脂肪酸是两种人体所需的重要营养物质。人体内的很多生理病理过程均涉及到这些多不饱和脂肪酸,以及它们在环氧合酶(cyclooxygenase,COX)和脂氧合酶(lipoxygenase,LOX)催化下产生的过氧化代谢物。环氧合酶和脂氧合酶催化的多不饱和脂肪酸的过氧化是复杂的生化过程,会产生一系列的自由基产物。这些自由基产物又会与蛋白质、DNA和RNA结合,从而导致很多生理功能的改变。然而一直以来,缺乏合适的分析方法来有效分离和鉴定这些自由基产物,限制了人们对环氧合酶和脂氧合酶,以及多不饱和脂肪酸的过氧化在生理作用方面的研究。直到最近,才出现了对COX/LOX催化产生的活泼自由基定性和定量分析的报道。这里将对一种可以用来鉴定体外脂类过氧化产生的自由基产物的自旋捕捉-LC/ESR/MS联用技术的发展与改进过程进行综述。这种新颖的LC/ESR/MS联用技术首次使得直接检测多不饱和脂肪酸代谢产生的自由基成为可能,这对自由基的生理学作用研究是一个重大突破,为人们在多不饱和脂肪酸的生理作用以及环氧合酶和脂氧合酶催化的脂质过氧化方面的研究带来了极大便利。 相似文献
17.
18.
Girotti AW 《Free radical biology & medicine》2008,44(6):956-968
Lipid hydroperoxides (LOOHs) generated in cells and lipoproteins under oxidative pressure may induce waves of damaging chain lipid peroxidation near their sites of origin if O2 is readily available and antioxidant capacity is overwhelmed. However, recent studies have demonstrated that chain induction is not necessarily limited to a nascent LOOH's immediate surroundings but can extend to other cell membranes or lipoproteins by means of LOOH translocation through the aqueous phase. Mobilization and translocation can also extend the range of LOOHs as redox signaling molecules and in this sense they could act like the small, readily diffusible inorganic analogue H2O2, which has been studied much more extensively in this regard. In this article, basic mechanisms of free-radical- and singlet-oxygen-mediated LOOH formation and one-electron and two-electron LOOH reduction pathways and their biological consequences are reviewed. The first studies to document spontaneous and protein-assisted LOOH transfer in model systems and cells are described. Finally, LOOH translocation is discussed in the context of cytotoxicity vs detoxification and expanded effector action, i.e., redox signaling activity. 相似文献
19.
M A Babizhayev 《Archives of biochemistry and biophysics》1988,266(2):446-451
Mechanisms underlying Ca2+ effects on lipid peroxidation (LPO) induced in liposomes (from egg yolk lecithin) and ufasomes (from linolenic acid and methyl linolenate) with the aid of an O2-(.) -generating system (Fe2+ + ascorbate) were studied. It was shown that stimulation of LPO by low Ca2+ concentrations (10(-6)-10(-5)M) was due to its ability to release Fe2+ ions bound to negatively charged (phosphate or carboxylic) lipid groups (of lecithin or linolenic acid), thus increasing the concentration of catalytically active Fe2+. The inhibitory effect of high Ca2+ concentrations was caused by its interaction with superoxide anion radicals and was not observed in LPO systems independent of O2- generation (e.g., Fe2+ + cumol hydroperoxide). 相似文献
20.
The free radicals generated from the iron containing system of xanthine oxidase and hypoxanthine (Fe-XO/HX) were directly detected by using spin trapping. It was found that not only superoxide anion (O(2)*-) and hydroxyl radical (OH*), but also alkyl or alkoxyl radicals (R*) were formed when saccharides such as glucose, fructose and sucrose were added into the Fe-XO/HX system. The generated amount of R* was dependent on the kind and concentration of saccharides added into the Fe-XO/HX system and no R* were detected in the absence of saccharides, indicating that there is an interaction between the saccharide molecules and the free radicals generated from the Fe-XO/HX system and saccharide molecules are essential for generating R* in the Fe-XO/HX system. It is expected that the toxicity of R* would be greater than of hydrophilic O(2)*- and OH* because they are liposoluble and their lives are longer and the active sites of biomolecules are closely related with lipophilic phase, thus they can damage cells more seriously than O(2)*- and OH*. The R* generated from the saccharide containing Fe-XO/HX can be effectively scavenged by selenium containing abzyme (Se-abzyme), indicating Se-abzyme is a promising antioxidant. 相似文献