Disease relevance of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• An in vitro Fenton system was established that generates DNA strand breaks and inactivates bacteriophage and that also reproduces the suppression of DNA damage by high concentrations of peroxide [1].
• Little is known about changes in the amount of iron in the intracellular low molecular weight pool, which catalyzes the Fenton reactions during reperfusion after ischemia [2].
• Inhaled silicate dusts may cause lung disease through their surface coordination of iron with subsequent oxidant generation via the Fenton reaction [3].
• A major portion of H2O2 toxicity is attributed to DNA damage caused by the iron-mediated Fenton reaction [4].
• These observations confirm unique renoprotective properties of ARB, independent of BP lowering but related to decreased oxidative stress (hydroxyl radicals scavenging and inhibition of the Fenton reaction), correction of chronic hypoxia, and inhibition of advanced glycation end product formation and of abnormal iron deposition [5].

Psychiatry related information on (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• Free radicals in disease pathogenesis, generated in part as a result of Fenton-type reactions, suggest that lowering the level of available iron, intervention with antioxidants, or the administration of free radical scavengers could provide a therapeutic inroad in the fight against Alzheimer's disease [6].
• The optimal reaction times in the Fenton and Photo-Fenton processes were 60 min and 80 min, respectively [7].

High impact information on (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• Toxic DNA damage by hydrogen peroxide through the Fenton reaction in vivo and in vitro [1].
• Prooxidant states can be caused by different classes of agents, including hyperbaric oxygen, radiation, xenobiotic metabolites and Fenton-type reagents, modulators of the cytochrome P-450 electron-transport chain, peroxisome proliferators, inhibitors of the antioxidant defense, and membrane-active agents [8].
• These findings suggest that asbestos inhalation can induce inducible nitric oxide synthase activation and peroxynitrite formation in vivo, and provide evidence of a possible alternative mechanism of asbestos-induced injury to that thought to be induced by Fenton reactions [9].
• The reactivity of H2O2 with iron (Fenton reaction) intimately connects oxidative stress and cellular iron metabolism [10].
• Thus, the localized Fenton reaction appears to impact the expression of hypoxia-regulated genes by means of HIF-1alpha stabilization and coactivator recruitment [11].

Chemical compound and disease context of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• Iron is of special interest because it may enhance tissue injury during ischemia and reperfusion by catalyzing the formation of highly reactive hydroxyl radicals (by modified Haber-Weiss or Fenton reactions) [12].
• Ferric nitrilotriacetate induces oxidative damage in renal proximal tubules, a consequence of Fenton-like reaction, that ultimately leads to a high incidence of renal cell carcinoma (RCC) in rats [13].
• Increased UHP in chronic renal failure enhances the formation of pentosidine and carboxymethyllysine via Fenton reaction (UHP-Fenton pathway) [14].
• The toxicity of paraquat (PQ2+) is attributed to intracellularly formed PQ*+, O(2)*-, H(2)O(2), and secondary.OH radicals generated through Fenton-like reactions [15].
• Killing of Bacillus subtilis spores by a modified Fenton reagent containing CuCl2 and ascorbic acid [16].

Biological context of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• By studying DNA damage during Fenton reactions in vitro, the same complex kinetics were observed and three types of oxidants were distinguished based upon their reactivities toward H2O2 and alcohols and upon iron-chelator effects [4].
• Thus, it was the aim of this study to localize the cellular compartment in which the Fenton reaction takes place and to determine whether scavenging of.OH can modulate hypoxia-inducible factor 1 (HIF-1)-dependent gene expression [11].
• The amino acid sequence of the rat ornithine carbamoyltransferase was compared with the recently reported sequence of the human enzyme [Horwich, A. L., Fenton, W. A., Williams, K. R., Kalousek, F., Kraus, J. P., Doolittle, R. F., Konigsberg, W. & Rosenberg, L. E. (1984) Science 224, 1068-1074] [17].
• Our previous characterization of the IL1B promoter indicated that the region between -131 and +12 is sufficient to direct cell-type-specific expression of a reporter gene (F. Shirakawa, K. Saito, C.A. Bonagura, D.L. Galson, M.J. Fenton, A.C. Webb, and P. E. Auron, Mol. Cell. Biol. 13:1332-1344, 1993) [18].
• These adducts are formed from lipid peroxidation products (F. El-Ghissassi et al., Chem. Res. Toxicol., 8: 273-283, 1995) and thus could arise in the liver of LEC rats from oxygen radicals generated by copper-catalyzed Fenton-type reactions [19].

Anatomical context of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• A Fenton reaction at the endoplasmic reticulum is involved in the redox control of hypoxia-inducible gene expression [11].
• During exposure to peroxide only, the iron in sickle membranes was unable to act as a Fenton catalyst without addition of a reducing agent [20].
• However, when we measured the Fenton chemistry educt hydrogen peroxide and its precursor, the superoxide anion radical, formation of both had markedly decreased and steady-state levels of hydrogen peroxide did not alter during cold incubation of either liver endothelial cells or hepatocytes [21].
• The results of this study demonstrated that the protection provided by DFO and other HAs against TCHQ-induced cyto- and genotoxicity in human fibroblasts is mainly through scavenging of the observed reactive TCSQ radical and not through prevention of the Fenton reaction by the binding of iron in a redox-inactive form [22].
• Fenton-like reactions may be commonly associated with most membranous fractions including mitochondria, microsomes, and peroxisomes [23].

Associations of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid with other chemical compounds

• In this study, we investigated whether iron, a potent source of the highly reactive hydroxyl radical that is generated by the Fenton reaction with H2O2, might contribute to the source of radicals in Alzheimer disease [24].
• In vitro and in vivo analyses showed that H(2)O(2) directly oxidized their solvent-exposed clusters in a Fenton-like reaction [25].
• Separate determinations of the two redox half-reactions involved (i.e. Fe3+ + O-.2----Fe2+ + O2 and Fe2+ + H2O2----Fe3+ + .OH + OH-) indicate that an available coordination site is necessary for the latter (Fenton) reaction [26].
• H2O2 alone decreases the viscosity of HA, presumably by the Fenton reaction, in the absence (but not in the presence) of the iron chelator, diethyltriaminepentacetic acid (DETAPAC) [27].
• To develop a method for estimating total HO. production, we studied two model systems: the superoxide driven Fenton reaction in vitro, using xanthine oxidase as the source of superoxide, and a computer model of Fenton chemistry [28].

Gene context of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• ESR spin-trapping studies demonstrated that GIF at 2-6 microm scavenged hydroxyl radicals generated by a Fenton-type reaction or the photolysis of hydrogen peroxide much more effectively than the same concentration of metallothionein I+II [29].
• Consistent with the damage specificity above, hSMUG1 removed damaged bases from Fenton-oxidized calf thymus DNA, generating abasic sites [30].
• The aconitase-released Fe(2+) combines with H(2)O(2) to generate *OH via a Fenton reaction and the oxidized Fe(3+) recombines with the inactivated enzyme after being reduced to Fe(2+) by other cellular reductants, turning it over to be active [31].
• These results suggest that PrPC modulates the intracellular H2O2 level as a copper-binding protein to protect CGNs from apoptotic cell death possibly due to inhibiting a Fenton reaction [32].
• Mechanisms of Saccharomyces cerevisiae PMA1 H+-ATPase inactivation by Fe2+, H2O2 and Fenton reagents [33].

Analytical, diagnostic and therapeutic context of (2R,3R,4S,5S)-2,3,4,5,6-pentahydroxyhexanoic acid

• The Fenton reaction could be localized in a perinuclear space by confocal laser microscopy and three-dimensional reconstruction techniques [34].
• CONCLUSIONS: The use of Fenton-like chemistry in SPIE-IA technology allows a sensitive measurement of E2 in human serum and could be a new approach for the development of sensitive immunoassays [35].
• The production of *OH in the supernatant of cultured rabbit corneal fibroblasts by the Fenton reaction caused an increase in PI (+) and TUNEL (+) cells by 90 minutes, which was significantly inhibited by the addition of DMSO [36].
• Similar Fenton-type treatment of the purine dinucleotides dApdG and dApdA resulted in products that were chromatographically identical on anion-exchange TLC and on reverse-phase HPLC to the two major products generated in DNA [37].
• Similar treatment of the double-stranded plasmid pBluescript K+ with hydrogen peroxide (1 mM) and each transition-metal ion (1-100 microM) followed by quantitative agarose gel electrophoresis demonstrated that open-circle DNA, resulting from single-strand breaks, was generated in Fenton reactions involving all nine metal ions [38].

References