Interaction Of HOCl Research Articles

Association of myeloperoxidase polymorphism (G463A) with cervix cancer.

Cervical cancer is the fourth most common cancer affecting women worldwide, according to the latest IARC release with 528 000 new cases every year. Infection by high-risk human papillomavirus (HPV) is necessary but not sufficient for progression to cancer. Epithelial tissues, the target of HPV infection, are heavily exposed to reactive oxygen species (ROS). Hypochlorous acid (HOCl) is a very potent ROS, and it is produced by myeloperoxidase (MPO). MPO, a lysosomal enzyme expressed in polymorphonuclear neutrophils (PMN), has the potential to kill HPV transformed cells, as a component of an intercellular induced-apoptosis pathway. This enzyme catalyzes the production of HOCl in the presence of hydrogen peroxide (H2O2). The H2O2 produced by the Doderlein's bacillus will interact with MPO, contributing to the intercellular induced-apoptosis pathway. We studied a functional polymorphism in the promoter region of MPO (G463A) and how it may affect the risk of developing cervix cancer. A sample of 100 patients with invasive cervical cancer and 122 control women were genotyped for MPO polymorphism by PCR-RFLP method. The statistical method used was χ(2). We found that women with the GG genotype had lower risk for cervical cancer than the women who displayed the heterozygous genotype GA (OR = 0.546, 95 % CI = 0.315-0.939, p = 0.028, OR = 2.210, 95 % CI = 1.257-3.886, p = 0.008, respectively). The genotype that leads to a higher concentration of ROS (GG) presents itself as a protection factor in comparison to the homozygous genotype (AA). This can be explained by the interaction of HOCl and superoxide of transformed cells that will generate apoptosis-inducing hydroxyl radicals.

Inhibition of Lung Fluid Clearance and Epithelial Na+ Channels by Chlorine, Hypochlorous Acid, and Chloramines

We investigated the mechanisms by which chlorine (Cl(2)) and its reactive byproducts inhibit Na(+)-dependent alveolar fluid clearance (AFC) in vivo and the activity of amiloride-sensitive epithelial Na(+) channels (ENaC) by measuring AFC in mice exposed to Cl(2) (0-500 ppm for 30 min) and Na(+) and amiloride-sensitive currents (I(Na) and I(amil), respectively) across Xenopus oocytes expressing human alpha-, beta-, and gamma-ENaC incubated with HOCl (1-2000 microm). Both Cl(2) and HOCl-derived products decreased AFC in mice and whole cell and single channel I(Na) in a dose-dependent manner; these effects were counteracted by serine proteases. Mass spectrometry analysis of the oocyte recording medium identified organic chloramines formed by the interaction of HOCl with HEPES (used as an extracellular buffer). In addition, chloramines formed by the interaction of HOCl with taurine or glycine decreased I(Na) in a similar fashion. Preincubation of oocytes with serine proteases prevented the decrease of I(Na) by HOCl, whereas perfusion of oocytes with a synthetic 51-mer peptide corresponding to the putative furin and plasmin cleaving segment in the gamma-ENaC subunit restored the ability of HOCl to inhibit I(Na). Finally, I(Na) of oocytes expressing wild type alpha- and gamma-ENaC and a mutant form of beta ENaC (S520K), known to result in ENaC channels locked in the open position, were not altered by HOCl. We concluded that HOCl and its reactive intermediates (such as organic chloramines) inhibit ENaC by affecting channel gating, which could be relieved by proteases cleavage.

RAW 264.7 macrophages induce apoptosis selectively in transformed fibroblasts: intercellular signaling based on reactive oxygen and nitrogen species

The rationale for this study was to determine whether macrophages induce apoptosis selectively in transformed compared with nontransformed fibroblasts and to elucidate the underlying intercellular signaling chemistry. Murine fibroblasts transformed by oncogene expression (ras, src) or methylcholanthrene treatment were sensitive for apoptosis induction by RAW 264.7 macrophages, whereas parental cells and revertants were insensitive. Moreover, RAW 264.7 macrophages induced apoptosis in normal rat kidney (NRK) fibroblasts transiently transformed by epidermal growth factor/transforming growth factor-beta. Sensitivity for intercellular apoptosis induction was based on target cell-derived superoxide anions and effector cell-derived peroxidase and nitric oxide (NO). Superoxide anions dismutate to hydrogen peroxide, which is converted to HOCl by the peroxidase. The interaction of HOCl with superoxide anions then generates hydroxyl radicals. In parallel, NO interacts with superoxide anions and generates apoptosis-inducing peroxynitrite. Signaling by reactive oxygen and nitrogen species seems to represent a hitherto unrecognized signaling principle for the selective elimination of potential tumor cells by macrophages.

Interaction of HOCl with a chlorinated ice surface to produce molecular chlorine: An ab-initio study

The reaction between molecular HOCl and a chlorinated surface of ice to produce molecular chlorine has been theoretically investigated. Ab initio quantum mechanical tools (GAUSSIAN 98 and EMBED01) have been used for this purpose, based on a molecular cluster and on an embedded cluster model, respectively. Different reaction paths have been explored, requiring a pre-activation of the substrate. In all cases, important activation barriers have been found. Only if certain types of structural defects are present at the surface, the reaction has been found to take place almost spontaneously.

Uptake of hydrochloric acid and hypochlorous acid onto sulfuric acid: solubilities, diffusivities, and reaction

The interaction of HOCl and HCl vapors with liquid sulfuric acid surfaces was studied in a flow tube equipped with chemical ionization mass spectrometry detection. Time-dependent uptake of HCl and HOCl was measured. A methodology for deriving the value of the quantity H[radical]D[sub 1], (the product of the Henry's law coefficient and the square root of the liquid-phase diffusion coefficient) is discussed. The partial pressures of HCl over HCl-doped sulfuric acid solutions were also measured to directly determine H for HCl (H[sub HCl]*). Using the measured values of H[sub HCl]* and H[sub HCl]*[radical]D[sub 1], the value of D[sub 1] for HCl in 50 wt % sulfuric acid was extracted. Values for H[sub HOCl] and for the second-order rate coefficient for the reaction between dissolved HOCl and HCl were also obtained. The application of these results to modeling stratospheric heterogeneous processes in sulfuric acid aerosols is discussed. 31 refs., 14 refs., 3 tabs.

Co-oxidation of luminol by hypochlorite and hydrogen peroxide implications for neutrophil chemiluminescence

Stimulated neutrophils produce several potent oxidants including H 2O 2, O 2 − and HOCl. Previous studies have revealed all of these compounds to be capable of oxidizing luminol, a reagent often used to indicate, by its chemiluminescence, the oxidative burst of neutrophils. Data presented in this paper indicate that H 2O 2 and HOCl spontaneously react at physiologic pH to produce luminol-dependent chemiluminescence 100 times the sum of the chemi luminescence of either reagent alone. This enhancement is due to a cooxidation by HOCl and H 2O 2, or to a novel oxidant generated by the interaction of HOCl and H 2O 2. The HOCl scavenger, taurine, inhibits the chemi luminescence. Evidence is presented against the participation of hydroxyl radical, O 2 − or singlet oxygen in the oxidation of luminol by HOCl and H 2O 2. These findings have implications for potential anti-inflamatory compounds.