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71.
John M. C. Gutteridge Melinda West Kent Eneff Robert A. Floyd 《Free radical research》1990,10(3):159-165
Bleomycin, in the presence of ferric salts, oxygen and a suitable reductant, degrades DNA with the release of base propenals, detected as thiobarbituric acid (TBA) reactivity, and the formation of 8-hydroxydeo-xyguanosine (80HdG) detected by HPLC. When xanthine oxidase is added to the incubated mixture of DNA degradation products, TBA-reactivity is destroyed but 80HdG formation is increased. EPR Spin trapping experiments show that hydroxyl radicals (OH) are formed in the reaction mixture and can be inhibited by the inclusion of either superoxide dismutase or catalase. These findings suggest that the base propenals and possibly malondialdehyde, formed from them, are aldehydic substrates for xanthine oxidase and, the product of this reaction is superoxide (O2-) and hydrogen peroxide (H2O2). Thus, TBA reactivity is destroyed in the formation of O2- and H2O2 which stimulate further oxidative damage to DNA resulting in increased 8OHdG formation. 相似文献
72.
Most carcinogens, including polycyclic aromatic hydrocarbons (PAH), require metabolic activation to produce the ultimate electrophilic species that bind covalently with cellular macromolecules to trigger the cancer process. Metabolic activation of PAH can be understood in terms of two main pathways: one-electron oxidation to yield reactive intermediate radical cations and monooxygenation to produce bay-region diol epoxides. The reason we have postulated that one-electron oxidation plays an important role in the activation of PAH derives from certain common characteristics of the radical cation chemistry of the most potent carcinogenic PAH. Two main features common to these PAH are: 1) a relatively low ionization potential, which allows easy metabolic removal of one electron, and 2) charge localization in the PAH radical cation that renders this intermediate specifically and efficiently reactive toward nucleophiles. Equally important, cytochrome P-450 and mammalian peroxidases catalyze one-electron oxidation. This mechanism plays a role in the binding of PAH to DNA. Chemical, biochemical and biological evidence will be presented supporting the important role of one-electron oxidation in the activation of PAH leading to initiation of cancer. 相似文献
73.
How to Characterize a Biological Antioxidant 总被引:15,自引:0,他引:15
Barry Halliwell 《Free radical research》1990,9(1):1-32
An antioxidant is a substance that, when present at low concentrations compared to those of an oxidizable substrate, significantly delays or prevents oxidation of that substrate. Many substances have been suggested to act as antioxidants in vivo, but few have been proved to do so. The present review addresses the criteria necessary to evaluate a proposed antioxidant activity. Simple methods for assessing the possibility of physiologically-feasible scavenging of important biological oxidants (superoxide, hydrogen peroxide, hydroxyl radical, hypochlorous acid, haem-associated ferryl species, radicals derived from activated phagocytes, and peroxyl radicals, both lipid-soluble and water-soluble) are presented, and the appropriate control experiments are described. Methods that may be used to gain evidence that a compound actually does function as an antioxidant in vivo are discussed. A review of the pro-oxidant and anti-oxidant properties of ascorbic acid that have been reported in the literature leads to the conclusion that this compound acts as an antioxidant in vivo under most circumstances. 相似文献
74.
萝卜离体子叶衰老与膜脂过氧化的关系 总被引:10,自引:0,他引:10
萝卜离体子叶在光下或暗中衰老及激素调节衰老过程中,作为叶片衰老指标的叶绿素和蛋白质含量的降低,发生在MDA含量增高之前,更早于SOD活性的下降。表明由SOD活性降低所导致的膜脂过氧化的增强,并非衰老的原初反应,而是叶片衰老到一定程度的生理变化。因此,至少在萝卜离体子叶上,不能将其衰老的启动归因于受SOD控制的膜脂过氧化作用导致的膜累积性质变。 相似文献
75.
There is increasing evidence that Ca2+ release from sarcoplasmic reticulum (SR) of mammalian skeletal muscle is regulated or modified by several factors including
ionic composition of the myoplasm. We have studied the effect of Cl− on the release of Ca2+ from the SR of rabbit skeletal muscle in both skinned psoas fibers and in isolated terminal cisternae vesicles. Ca2+ release from the SR in skinned fibers was inferred from increases in isometric tension and the amount of release was assessed
by integrating the area under each tension transient. Ca2+ release from isolated SR was measured by rapid filtration of vesicles passively loaded with 45Ca2+. Ca2+ release from SR was stimulated in both preparations by exposure to a solution containing 191 mm choline-Cl, following pre-equilibration in Ca2+-loading solution that had propionate as the major anion. Controls using saponin (50 μg/ml), indicated that the release of
Ca2+ was due to direct action of Cl− on the SR rather than via depolarization of T-tubules. Procaine (10 mm) totally blocked Cl−- and caffeine-elicited tension transients recorded using loading and release solutions having ([Na+] + [K+]) × [Cl−] product of 6487.69 mm
2 and 12361.52 mm
2, respectively, and blocked 60% of Ca2+ release in isolated SR vesicles. Surprisingly, procaine had only a minor effect on tension transients elicited by Cl− and caffeine together. The data from both preparations suggests that Cl− induces a relatively small amount of Ca2+ release from the SR by activating receptors other than RYR-1. In addition, Cl− may increase the Ca2+ sensitivity of RYR-1, which would then allow the small initial release of Ca2+ to facilitate further release of Ca2+ from the SR by Ca2+-induced Ca2+ release.
Received: 6 February 1996/Revised: 17 July 1996 相似文献
76.
The prokaryotic endosymbionts that became plastids and mitochondria contained genes destined for one of three fates. Genes
required for free-living existence were lost. Most genes useful to the symbiosis were transferred to the nucleus of the host.
Some genes, a small minority, were retained within the organelle. Here we suggest that a selective advantage of movement of
genes to the nucleus is decreased mutation: plastids and mitochondria have high volume-specific rates of redox reactions,
producing oxygen free radicals that chemically modify DNA. These mutations lead to synthesis of modified electron carriers
that in turn generate more mutagenic free radicals—the “vicious circle” theory of aging. Transfer of genes to the nucleus
is also advantageous in facilitating sexual recombination and DNA repair. For genes encoding certain key components of photosynthesis
and respiration, direct control of gene expression by redox state of electron carriers may be required to minimize free radical
production, providing a selective advantage of organelle location which outweighs that of location in the nucleus. A previous
proposal for transfer of genes to the nucleus is an economy of resources in having a single genome and a single apparatus
for gene expression, but this argument fails if any organellar gene is retained. A previous proposal for the retention of
genes within organelles is that certain proteins are organelle-encoded because they cannot be imported, but there is now evidence
against this view. Decreased free radical mutagenesis and increased sexual recombination upon transfer to the nucleus together
with redox control of gene expression in organelles may now account for the slightly different gene distributions among nuclei,
plastids, and mitochondria found in major eukaryote taxa. This analysis suggests a novel reason for uniparental inheritance
of organelles and the evolution of anisogametic sex, and may also account for the occurrence of nitrogen fixation in symbionts
rather than in nitrogen-fixing organelles.
Correspondence to: J.F. Allen 相似文献
77.
Abstract: Activated microglia, often associated with neuritic amyloid plaques in the Alzheimer's disease brain, are likely to contribute to the progression of the disease process, e.g., by releasing neurotoxic reactive oxygen and/or nitrogen intermediates. In the present study, whether the amyloid β peptide (Aβ), the principal constituent of amyloid plaques, can stimulate microglial respiratory burst activity and/or microglial production of nitric oxide was examined. Using neonatal rat microglial cultures as a model, it was found that neither the spontaneous release of nitric oxide nor the lipopolysaccharide-induced production of nitric oxide was altered in cultures previously incubated with synthetic Aβ(1–40). for 24 h. In addition, no direct stimulatory effect of Aβ(1–40) on the respiratory burst activity was observed. Nevertheless, concomitant with an increase in the number of responsive cells, a profound priming of the phorbol 12-myristate 13-acetate-evoked production of superoxide anion was observed in Aβ(1–40)-treated cultures. Thus, both the maximal rate and the total phorbol 12-myristate 13-acetate-induced production of superoxide appeared to be statistically significantly higher as compared with untreated cultures. It is concluded that, as far as activation of the microglial respiratory burst is concerned, Aβ(1–40) may merely act as a priming rather than a triggering stimulus. 相似文献
78.
79.
Ma Rosario de la Torre Angela Casado Ma Encarnación López-Fernández Diana Carrascosa Ma Concepción Casado Domenico Venarucci Vincenzo Venarucci 《Neurochemical research》1996,21(8):885-888
In order to investigate the role of two free radical detoxificant enzymes in patients with aging brain disorders, superoxide
dismutase (SOD) and catalase (CAT) activities have been measured in blood from male and female human patients of different
ages with several types of aging brain disorders. When compared with activities in the normal population, we have detected:
1) SOD and CAT activities are decreased in patients with Parkinson disease. 2) SOD activity seems to be normal and CAT activity
is decreased in patients with dementia. 3) In the patients with stroke, SOD activity is normal, while CAT activity is decreased.
SOD activity was measured in red blood cells using the Minami and Yoshikawa method. CAT activity was measured in hemolysates
by the method of Aebi. We can conclude that SOD and CAT activities in patients with Parkinson disease are decreased. 相似文献
80.
The mitochondrial inner membrane anion channel (IMAC) is a channel, identified by flux studies in intact mitochondria, which has a broad anion selectivity and is maintained closed or inactive by matrix Mg2+ and H+. We now present evidence that this channel, like many other chloride/anion channels, is reversibly blocked/inhibited by stilbene-2,2-disulfonates. Inhibition of malonate transport approaches 100% with IC50 values of 26, 44, and 88 M for DIDS, H2-DIDS, and SITS respectively and Hill coefficients 1. In contrast, inhibition of Cl– transport is incomplete, reaching a maximum of about 30% at pH 7.4 and 65% at pH 8.4 with an IC50 which is severalfold higher than that for malonate. The IC50 for malonate transport is decreased about 50% by pretreatment of the mitochondria withN-ethylmaleimide. Raising the assay pH from 7.4 to 8.4 increases the IC50 by about 50%, but under conditions where only the matrix pH is made alkaline the IC50 is decreased slightly. These properties and competition studies suggest that DIDS inhibits by binding to the same site as Cibacron blue 3GA. In contrast, DIDS does not appear to compete with the fluorescein derivative Erythrosin B for inhibition. These findings not only provide further evidence that IMAC may be more closely related to other Cl– channels than previously thought, but also suggest that other Cl– channels may be sensitive to some of the many regulators of IMAC which have been identified. 相似文献