scholarly journals THE RELATIONSHIP OF HYDROGEN PEROXIDE TO THE INHIBITION OF THE GLYOXALASE ACTIVITY OF INTACT ERYTHROCYTES BY X-RADIATION

1958 ◽  
Vol 41 (4) ◽  
pp. 737-753 ◽  
Author(s):  
S. J. Klebanoff

The x-irradiation of a dilute suspension of erythrocytes results in a decrease in the glyoxalase activity of the cells as a result of a fall in the reduced glutathione level. The present paper deals with the possible role of H2O2 in this reaction. The addition of intact erythrocytes to physiological saline previously irradiated with 150,000 r or 225,000 r results in a fall in the glyoxalase activity of the cells. The inhibition is prevented by the preincubation of the irradiated saline with catalase and is reversed by the addition of plasma, glucose, adenosine, and inosine to the cell suspension. An inhibition of the glyoxalase activity is also produced by the addition of H2O2 to the suspension of erythrocytes. The inhibitory effect of H2O2 can be prevented and largely reversed by plasma, glucose, adenosine, and inosine. Methylglyoxal is also protective under these conditions. Hydrogen peroxide formed continuously and in low concentrations by enzyme systems appears to be more effective than added H2O2 in inhibiting the glyoxalase system. The inhibition by H2O2-producing enzyme systems is minimized by the addition of catalase, plasma, glucose, methylglyoxal, and to a lesser extent, by adenosine and inosine, and is accentuated by the addition of sodium azide. The results are discussed in relation to the role of H2O2 and catalase in the toxicity of ionizing radiations.

1958 ◽  
Vol 41 (4) ◽  
pp. 725-736 ◽  
Author(s):  
S. J. Klebanoff

The x-irradiation of intact washed erythrocytes results in an inhibition of the glyoxalase activity of the cells chiefly as a result of a decrease in the reduced glutathione level. The percentage inhibition is markedly increased by an increase in the dilution of the cells in physiological saline suggesting that the effect of radiation is indirect, via the production in the aqueous medium of free radicals, H2O2, etc. This is supported by the decrease in the inhibition produced by lowering the oxygen tension or by the addition of catalase. The inhibition of glyoxalase activity is also decreased by the addition of methylglyoxal, plasma, adenosine, inosine, glucose, and a number of other sugars to the erythrocyte suspension prior to radiation. Furthermore, some reactivation of the glyoxalase system results from the addition of plasma, glucose, adenosine, and inosine following radiation. These results are discussed in relation to the role of SH compounds, particularly glutathione, in the toxicity of ionizing radiations.


2014 ◽  
Vol 2014 ◽  
pp. 1-5 ◽  
Author(s):  
Halyna M. Semchyshyn

The biphasic-dose response of microorganisms to hydrogen peroxide is a phenomenon of particular interest in hormesis research. In different animal models, the dose-response curve for ethanol is also nonlinear showing an inhibitory effect at high doses but a stimulatory effect at low doses. In this study, we observed the hormetic-dose response to ethanol in budding yeastS. cerevisiae. Cross-protection is a phenomenon in which exposure to mild stress results in the acquisition of cellular resistance to lethal stress induced by different factors. Since both hydrogen peroxide and ethanol at low concentrations were found to stimulate yeast colony growth, we evaluated the role of one substance in cell cross-adaptation to the other substance as well as some weak organic acid preservatives. This study demonstrates that, unlike ethanol, hydrogen peroxide at hormetic concentrations causes cross-resistance ofS. cerevisiaeto different stresses. The regulatory protein Yap1 plays an important role in the hormetic effects by low concentrations of either hydrogen peroxide or ethanol, and it is involved in the yeast cross-adaptation by low sublethal doses of hydrogen peroxide.


Blood ◽  
1956 ◽  
Vol 11 (1) ◽  
pp. 1-10 ◽  
Author(s):  
AUSTIN S. WEISBERGER ◽  
LEIF G. SUHRLAND ◽  
JOSEPH SEIFTER

Abstract The amino acids L-cysteine and L-cystine appear to have an important role in the metabolism of leukocytes. Decreased availability of these amino acids may therefore have important effects on leukocytes. The possibility of decreasing the influx of radioactive L-cystine into leukemic leukocytes was investigated by exposing the leukocytes to various analogues of cysteine (cystine) prior to incubation with S35 L-cystine. It was found that a highly specific structural and spatial configuration is required to decrease the influx of S35 L-cystine. Thus unlabeled L-cysteine is effective in decreasing the incorporation of radioactive L-cystine. However, analogues of cystine in which there is modification or substitution of the sulfhydryl, amino or carboxyl group do not decrease the influx of S35 L-cystine. Furthermore, any alteration in the spatial relationship of the sulfhydryl and amino groups of L-cysteine also results in a loss of the ability of an analogue to decrease the incorporation of S35 L-cystine. Of the compounds studied and in the concentrations employed, only unlabeled L-cysteine, selenium cystine and phenyl selenium cysteine were effective. Selenium cystine is identical with cystine except that selenium replaces the sulfur in the molecule. Phenyl selenium cysteine is also closely related structurally to cysteine. The mechanism of action of selenium cystine and phenyl selenium cysteine in decreasing the influx of S35 L-cystine is not known. Other selenium compounds tested were ineffective. These compounds may exert their inhibitory effect by (a) competitive combination with specific intracellular receptors for L-cysteine (L-cystine), (b) inactivation of enzymes or compounds essential for normal cellular function, (c) alteration in membrane permeability or (d) a toxic effect of selenium. Since selenium cystine and phenyl selenium cystine are inhibitory in low concentrations in vitro, these compounds may have important effects on leukemic leukocytes in vivo.


1994 ◽  
Vol 40 (3) ◽  
pp. 219-227 ◽  
Author(s):  
Nobuhiko ARAKAWA ◽  
Shino NEMOTO ◽  
Emiko SUZUKI ◽  
Megumi OTSUKA

2017 ◽  
Vol 313 (2) ◽  
pp. F254-F261 ◽  
Author(s):  
Lijun Wang ◽  
Chengbiao Zhang ◽  
Xiao-Tong Su ◽  
Dao-Hong Lin ◽  
Peng Wu ◽  
...  

Our aim is to examine the role of PGF2α receptor (FP), a highly expressed prostaglandin receptor in the distal convoluted tubule (DCT) in regulating the basolateral 40-pS K channel. The single-channel studies demonstrated that PGF2α had a biphasic effect on the 40-pS K channel in the DCT–PGF2α stimulated at low concentrations (less than 500 nM), while at high concentrations (above 1 µM), it inhibited the 40-pS K channels. Moreover, neither 13,14-dihydro-15-keto-PGF2α (a metabolite of PGF2α) nor PGE2 was able to mimic the effect of PGF2α on the 40-pS K channel in the DCT. The inhibition of PKC had no significant effect on the 40-pS K channel; however, it abrogated the inhibitory effect of 5 µM PGF2α on the K channel. Moreover, stimulation of PKC inhibited the 40-pS K channel in the DCT, suggesting that PKC mediates the inhibitory effect of PGF2α on the 40-pS K channel. Conversely, the stimulatory effect of PGF2α on the 40-pS K channel was absent in the DCT treated with DPI, a NADPH oxidase (NOX) inhibitor. Also, adding 100 µM H2O2 mimicked the stimulatory effect of PGF2α and increased the 40-pS K channel activity in DCT. Moreover, the stimulatory effect of 500 nM PGF2α and H2O2 was not additive, suggesting the role of superoxide-related species in mediating the stimulatory effect of PGF2α on the 40-pS K channel. The inhibition of Src family tyrosine protein kinase (SFK) not only inhibited the 40-pS K channel in the DCT but also completely abolished the stimulatory effects of PGF2α and H2O2 on the 40-pS K channel. We conclude that PGF2α at low doses stimulates the basolateral 40-pS K channel by a NOX- and SFK-dependent mechanism, while at high concentrations, it inhibits the K channel by a PKC-dependent pathway.


2013 ◽  
Vol 67 (3) ◽  
pp. 419-426
Author(s):  
Vladan Djuric ◽  
Nebojsa Deletic ◽  
Vesna Stankov-Jovanovic ◽  
Ranko Simonovic

Primary role of peroxidase enzyme is to decompose endogenous hydrogen peroxide, when oxygen radical is being replaced by a less potent radical, which is its cosubstrates oxidized form. During this study, catalytic activity of horseradish peroxidase has been observed in the presence of antioxidants from vitamin group, such as C, E and A, i.e. their water-soluble forms. It was found that vitamin E showed no effect on the enzyme activity and fate of cosubstrate radicals from the group of benzidine derivatives. Vitamin C proceeds enzymatic reaction showing its antioxidative character, and absorbs electrons from radicals, bringing cosubstrate back to its relaxed state. On the other hand, vitamin A plays a role of uncompetitive peroxidase inhibitor, which is visible through decreasing initial rate of catalytic reaction, and is reflected as virtual decrease of enzyme concentration. Furthermore, it prolongs life of endogenous hydrogen peroxide, which could potentially lead to oxidative stress of cells. This inhibitory effect can be used in analytical purpose, for determination of retinol acetate content in a sample.


2013 ◽  
Vol 26 (1) ◽  
pp. 106-115 ◽  
Author(s):  
Kamrun Nahar ◽  
Tina Kyndt ◽  
Bettina Hause ◽  
Monica Höfte ◽  
Godelieve Gheysen

The importance of phytohormone balance is increasingly recognized as central to the outcome of plant–pathogen interactions. Next to their well-known developmental role, brassinosteroids (BR) were recently found to be involved in plant innate immunity. In this study, we examined the role of BR in rice (Oryza sativa) innate immunity during infection with the root-knot nematode Meloidogyne graminicola, and we studied the inter-relationship with the jasmonate (JA) pathway. Exogenous epibrassinolide (BL) supply at low concentrations induced susceptibility in the roots whereas high concentrations of BL enforced systemic defense against this nematode. Upon high exogenous BL supply on the shoot, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) confirmed a strong feedback inhibitory effect, leading to reduced BR biosynthesis in the root. Moreover, we demonstrate that the immune suppressive effect of BR is at least partly due to negative cross-talk with the JA pathway. Mutants in the BR biosynthesis or signaling pathway accumulate slightly higher levels of the immediate JA-precursor 12-oxo-phytodienoic acid, and qRT-PCR data showed that the BR and JA pathway are mutually antagonistic in rice roots. Collectively, these results suggest that the balance between the BR and JA pathway is an effective regulator of the outcome of the rice–M. graminicola interaction.


2002 ◽  
Vol 283 (6) ◽  
pp. H2620-H2626 ◽  
Author(s):  
Michela Zanetti ◽  
Zvonimir S. Katusic ◽  
Timothy O'Brien

Although hydrogen peroxide (H2O2) induces proliferation of vascular smooth muscle cells, its role in endothelial cell proliferation is unclear. Our aim was to study the role of hydrogen peroxide in endothelial cell proliferation by overexpressing catalase. Human aortic endothelial cells were transduced with adenoviral vectors encoding β-galactosidase (Adβgal) or catalase (AdCat) or were exposed to diluent alone (control). Transgene expression was demonstrated by β-galactosidase staining, Western analysis, and significantly increased enzyme activity in AdCat-transduced cells. Overexpression of catalase decreased DNA synthesis in AdCat compared with control and Adβgal-transduced cells (536.8 ± 31 vs. 1,875.1 ± 132.9 vs. 1,347.5 ± 93.7 dpm/well, respectively; P < 0.05 vs. control and Adβgal). Six days after transduction with AdCat (multiplicity of infection = 50), cell numbers were significantly reduced (AdCat: 38 ± 1.8% of cell counts in control, P < 0.05; and 45 ± 2% of cell count in Adβgal, P < 0.05). Incubation with aminotriazole 10 mmol/l, an inhibitor of catalase, prevented this effect. The number of apoptotic cells was increased one- and threefold 2 and 4 days, respectively, after transduction with AdCat. Exogenous administration of low concentrations of H2O2(50 μM) significantly increased cell proliferation, whereas it was inhibited by higher concentrations. These results suggest that H2O2 is an important modulator of endothelial cell proliferation.


Development ◽  
2002 ◽  
Vol 129 (3) ◽  
pp. 681-693 ◽  
Author(s):  
Hui Fu ◽  
Yingchuan Qi ◽  
Min Tan ◽  
Jun Cai ◽  
Hirohide Takebayashi ◽  
...  

In this study, we have investigated the relationship of Olig2+ and Nkx2.2+ oligodendrocyte progenitors (OLPs) by comparing the expression of Olig2 and Nkx2.2 in embryonic chicken and mouse spinal cords before and during the stages of oligodendrogenesis. At the stages of neurogenesis, Olig2 and Nkx2.2 are expressed in adjacent non-overlapping domains of ventral neuroepithelium. During oligodendrogenesis stages, these two domains generate distinct populations of OLPs. From the Olig2+ motoneuron precursor domain (pMN) arise the Olig2+/Pdgfra+ OLPs, whereas the Nkx2.2+ p3 domain give rise to Nkx2.2+ OLPs. Despite their distinct origins, both populations of OLPs eventually appear to co-express Olig2 and Nkx2.2 in the same cells. However, there is a species difference in the timing of acquiring Nkx2.2 expression by the Olig2+/Pdgfra+ OLPs. The co-expression of Nkx2.2 and Olig2 in OLPs is tightly associated with myelin gene expression in the normal and PDGFA–/– embryos, suggesting a cooperative role of these transcription factors in the control of oligodendrocyte differentiation. In support of this suggestion, inhibition of expression of these two transcription factors in culture by antisense oligonucleotides has an additive inhibitory effect on OLP differentiation and proteolipid protein (PLP) gene expression.


2001 ◽  
Vol 69 (1) ◽  
pp. 378-385 ◽  
Author(s):  
Didier Heumann ◽  
Yoshiyuki Adachi ◽  
Didier Le Roy ◽  
Naohito Ohno ◽  
Toshiro Yadomae ◽  
...  

ABSTRACT Plasma lipopolysaccharide (LPS)-binding protein (LBP) and membrane CD14 function to enhance the responses of monocytes to low concentrations of endotoxin. Surprisingly, recent reports have suggested that LBP or CD14 may be dispensable for macrophage responses to low concentrations of LPS or may even exert an inhibitory effect in the case of LBP. We therefore investigated whether LBP and CD14 participated in the response of mouse peritoneal exudate macrophages (PEM) to LPS stimulation. In the presence of a low amount of plasma (<1%) or of recombinant mouse or human LBP, PEM were found to respond to low concentrations of LPS (<5 to 10 ng/ml) in an LBP- and CD14-dependent manner. However, tumor necrosis factor production (not interleukin-6 production) by LPS-stimulated PEM was reduced when cells were stimulated in the presence of higher concentrations of plasma or serum (5 or 10%). Yet, the inhibitory effect of plasma or serum was not mediated by LBP. Taken together with previous results obtained withLBP and CD14 knockout mice in models of experimental endotoxemia, the present data confirm a critical part for LBP and CD14 in innate immune responses of both blood monocytes and tissue macrophages to endotoxins.


Sign in / Sign up

Export Citation Format

Share Document