Characterization of a phospholipase A2 in hamster lung and in vitro and in vivo effects of bleomycin on this enzyme

Oh²,

Bulletin of the Korean Chemical Society

et al. 2012

Fenton reaction and iron autoxidation have been debated for the major process in ROS mediated DNA cleavage. We compared both processes on iron oxidation, DNA cleavage, and cyclic voltammetric experiment at different pHs. Both oxidation reactions were preferred at basic pH condition, unlike DNA cleavage. This indicates that iron oxidation and the following steps probably occur separately. The ROS generated from autoxidation seems to be superoxide radical since sod exerted the best inhibition on DNA cleavage when H2O2 was absent. In comparison of cyclic voltammograms of Fe 2+ in NaCl solution and phosphate buffer, DNA addition to phosphate buffer induced significant change in the redox cycle of iron, indicating that iron may bind DNA as a complex with phosphate. Different pulse voltammogram in the presence of ctDNA suggest that iron ions are recyclable at acidic pH, whereas they may form an electrically stable complex with DNA at high pH condition.

Section: Discussionmentioning

confidence: 99%

Section: +mentioning

confidence: 99%

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Effect of pH on the Iron Autoxidation Induced DNA Cleavage

Oh²,

Bulletin of the Korean Chemical Society

et al. 2012

Environ Health Perspect

“…Calcium also stimulates phospholipase-A2, a rate-limiting enzyme, in the metabolism of arachidonic acid. Metabolites of arachidonic acid appear to be involved in the BL-induced lung fibrosis (75). Activation of PIA2 stimulates the peroxidation of membrane lipids (76) that is measured by the amount of MDAE.…”

Section: Discussionmentioning

confidence: 99%

“…The hamsters were randomly placed into four treatment groups: saline-instilled fed control diet (SA), bleomycin-instilled fed control diet (BL), bleomycin-instilled fed taurine-niacin in diet (TNBL), and saline-instilled fed taurine-niacin in diet (TNSA). The animals were intratracheally instilled with either three consecutive doses of bleomycin sulfate in saline, or saline 1 week apart (2.5, 2.0, and 1.5 U/5 ml/kg) under pentobarbital anesthesia (75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85) mg/kg) as described by Zia et al (14).…”

Section: Methodsmentioning

confidence: 99%

Amelioration of bleomycin-induced lung fibrosis in hamsters by dietary supplementation with taurine and niacin: biochemical mechanisms.

Giri

Blaisdell

Rucker

et al. 1994

Interstitial pulmonary fibrosis induced by intratracheal instillation of bleomycin (BL) involves an excess production of reactive oxygen species, unavailability of adequate levels of NAD and ATP to repair the injured pulmonary epithelium, and an overexuberant lung collagen reactivity followed by deposition of highly cross-linked mature collagen fibrils resistant to enzymatic degradation. In the present study, we have demonstrated that dietary supplementation with taurine and niacin offered almost complete protection against the lung fibrosis in a multidose BL hamster model. The mechanisms for the protective effect of taurine and niacin are multifaceted. These include the ability of taurine to scavenge HOCI and stabilize the biomembrane; niacin's ability to replenish the BL-induced depletion of NAD and ATP; and the combined effect of taurine and niacin to suppress all aspects of BL-induced increases in the lung collagen reactivity, a hallmark of interstitial pulmonary fibrosis. It was concluded from the data presented at this Conference that the combined treatment with taurine and niacin, which offers a multipronged approach, will have great therapeutic potential in the intervention of the development of chemically induced interstitial lung fibrosis in animals and humans. -Environ Health Perspect 102(Suppl 10): 137-148 (1994)

Effect of Various Intercalators on the Fenton‐Type Oxidative Cleavage of Double‐Stranded DNA

Sung

Chemistry An Asian Journal

et al. 2014

The intensity of the linear dichroism (LD) in the absorption region of DNA (about 260 nm) decreased with time in the presence of [Fe(EDTA)](2+) (EDTA = ethylenediaminetetraacetic acid), H2O2, and ascorbate. The decrease in the LD signal indicated either an increase in flexibility, a shortening of the DNA stem, or both, owing to oxidative cleavage, and was best described by the difference between the two single-exponential-decay curves, thereby suggesting the involvement of two sequential first-order reactions. The fast reaction was assigned to cleavage of one of two DNA strands, which increased the flexibility of the DNA. The slow reaction corresponded to cleavage at or near the first cleavage site, thereby shortening the DNA stem. The presence of an intercalator, including ethidium, propidium, 9-aminoacridine, and proflavine, inhibited the first step of the cleavage reaction. One of the possible reasons for the observed inhibition might be a change in the DNA conformation near the intercalation site. Intercalation caused an unwinding and elongation of the DNA and resulted in changes in the location of the H atoms of the sugar moiety, which is known to be the main site at which hydroxyl radicals react.