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Biomedical subjects

E Capuozzo

Publications and source records attributed to E Capuozzo.

At least 19 recordsLinked to original sources
PubMed2005

Inhibition of ion transport ATPases by HNE.

4-Hydroxy-2,3-trans-nonenal (HNE), a major lipid peroxidation product, has been shown to react with specific amino acid residues of proteins and alter their function. In vitro exposure of erythrocyte ghosts and neutrophil membranes to HNE results in the inhibition of ion transport ATPases. Neutrophil membrane Ca2+-ATPase is strongly inhibited by micromolar concentrations of HNE, while HNE is considerably less effective against neutrophil Mg2+-ATPase and the erythrocyte ghost enzymes.

Adenosine Triphosphatases↗
PubMed2005

Effect of carotenoid oxidation products on neutrophil viability and function.

Human neutrophils are short-lived cells that play important roles in host defense and acute inflammation by releasing hydrolytic and cytotoxic proteins and reactive oxygen derivatives. Apoptosis, a physiological mechanism for cell death, regulates both production and survival of neutrophils, representing a basic biological mechanism for this type of cells. Carotenoids may react with toxic oxygen metabolites released by neutrophils to form a multitude of carotenoid cleavage products that exert, in turn, relevant prooxidative biological effects. Recent data suggest that carotenoid oxidation products may affect neutrophil viability and function by exerting proapoptotic activity and interfering with superoxide production by activated cells. The prooxidant and proapoptotic activities of carotenoid oxidation products could account, at least in some cases, for the procancerogenic properties of carotenoid rich diet.

Apoptosis↗
PubMed2003

High sensitivity of plasma membrane ion transport ATPases from human neutrophils towards 4-hydroxy-2,3-trans-nonenal.

Lipid peroxidation results in release of 4-hydroxy-2,3-trans-nonenal (HNE), which is known to conjugate to specific amino acids of proteins and may alter their function. The effect of HNE on the activities of Na(+)/K(+)-ATPase, Mg(2+)-ATPase, Ca(2+)-ATPase, and calmodulin-stimulated Ca(2+)-ATPase has been studied both in erythrocyte ghosts and in neutrophil membrane preparations. Neutrophil Ca(2+)-ATPase was strongly inhibited by micromolar concentrations of HNE (IC(50) = 12 microM), that means in the range of pathophysiologically relevant HNE levels. The IC(50) value for neutrophil Na(+)/K(+)-ATPase was about 40 microM. HNE was considerably less effective against neutrophil Mg(2+)-ATPase and the erythrocyte ghost enzymes (IC(50) values range from 91 to 240 microM). The data suggest that HNE may play a specific role in the regulation of neutrophil calcium homeostasis in response to oxidative stress.

Adenosine Triphosphatases↗
PubMed1997

Effects of calmodulin antagonists on calcium pump and cytosolic calcium level in human neutrophils.

The concentration of cytosolic free calcium was monitored in suspensions of intact human neutrophils in phosphate-buffered saline by means of the fluorescent indicator Indo 1 trapped in the cytosol. Trifluoperazine and n-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide markedly reduced the amplitude of the transient increase in cytosolic Ca2+ triggered by CaCl2 as well as by N-formyl-methionyl-leucyl-phenylalanine. The effect of the calmodulin antagonists on the calcium burst observed upon cell activation was much more pronounced in the presence of extracellular free calcium than in EGTA-containing media; it was not inhibited by wortmannin or thapsigargin. Nevertheless, trifluoperazine and n-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide inhibited the plasma-membrane Ca2+ ATPase if added to plasma membrane-enriched fractions of neutrophils. These results suggest that calmodulin antagonists affect calcium ion influx even if they inhibit plasma membrane Ca2+ ATPase.

Calcium↗
PubMed1997

The interaction of a new anti-tumour drug, KAR-2 with calmodulin.

1. KAR-2 (3"-(beta-chloroethyl)-2",4"-dioxo-3,5" -spiro-oxazolidino-4-deacetoxy-vinblastine) is a semisynthetic bis-indol derivative, with high anti-microtubular and anti-tumour activities but with low toxicity. KAR-2, in contrast to other biologically active bis-indols (e.g. vinblastine) did not show anti-calmodulin activity in vitro (enzyme kinetic, fluorescence anisotropy and immunological tests). 2. Direct binding studies (fluorescence resonance energy transfer, circular dichroism) provided evidence for the binding of KAR-2 to calmodulin. The binding affinity of KAR-2 to calmodulin (dissociation constant was about 5 microM) in the presence of Ca2+ was comparable to that of vinblastine. 3. KAR-2 was able to interact with apo-calmodulin as well; in the absence of Ca2+ the binding was of cooperative nature. 4. The effect of drugs on Ca2+ homeostasis in human neutrophil cells was investigated by means of a specific fluorescent probe. Trifluoperazine extensively inhibited the elevation of intracellular Ca2+ level, vinblastine did not appreciably affect it, KAR-2 stimulated the Ca2+ influx and after a transient enhancement the Ca2+ concentration reached a new steady-state level. 5. Comparison of the data obtained with KAR-2 and bis-indols used in chemotherapy suggests that the lack of anti-calmodulin potency resides on the spiro-oxazolidino portion of KAR-2. This character of KAR-2 manifested itself in various systems and might result in its low in vivo toxicity, established in an anti-tumour test.

Animals↗
PubMed1997

Inhibition of NADPH oxidase-mediated superoxide radical formation in PMA-stimulated human neutrophils by 4-hydroxynonenal--binding to -SH and -NH2 groups.

4-Hydroxynonenal (HNE), a major lipid peroxidation product, effectively inhibits the superoxide radical formation by NADPH oxidase of phorbol myristate acetate (PMA)--stimulated human PMNL. The I50 value for the inhibition of NADPH oxidase-mediated superoxide radical formation by 4-hydroxynonenal was found to be 19 microM. The HNE inhibition involves the reaction with both -SH and -NH2 groups. Superoxide formation as final result of the NADPH oxidase cascade was almost completely restored by addition of dithiothreitol. In presence of hydroxylamine only a minor restoration of superoxide radical formation was found. A combination of dithiothreitol and hydroxylamine yielded the greatest recovery. Two other aldehydes with the same chain length as HNE but different binding to lysine, histidine and cysteine residues, trans-2,3-nonenal and nonanal, gave I50 values for the inhibition of NADPH oxidase-mediated superoxide formation rate of 110 microM or > 300 microM, respectively.

Aldehydes↗
PubMed1993

Polyene antibiotics inhibit superoxide-producing NADPH oxidase in a polymorphonuclear cell-free system.

We studied the effect of polyene macrolide antibiotics on the NADPH-dependent superoxide production induced by arachidonic acid in a cell-free system consisting of the membrane and cytosolic fractions obtained from bovine polymorphonuclear leukocytes. Preincubation of the membrane fraction with polyenes before addition of the soluble components of the reaction mixture resulted in a dose-dependent inhibition of superoxide production.

Animals↗
PubMed1993

Adenosine affects the f-met-leu-phe induced changes in cytosolic Ca2+ and in membrane potential of human granulocytes.

Indo 1 acetoxymethyl ester and 3,3-dipentyloxacarbocyanine iodide have been used to investigate the effect of adenosine on the changes in cytosolic Ca2+ concentration and in membrane potential of human granulocytes activated by the chemotactic tripeptide f-met-leu-phe. Adenosine does not significantly affect negative (hyperpolarizing) potential changes as well as calcium accumulation in cytosol, whereas both the amplitude of the depolarization phase and the relaxation time for restoring the initial intracellular calcium level are reduced.

Adenosine↗
PubMed1991

Valinomycin-induced modulation of adriamycin resistance and cationic probe distribution in MCF-7 cell lines.

In vitro restoration of adriamycin sensitivity in a resistant human breast tumor cell line was obtained by continuous exposure to nanomolar nontoxic valinomycin concentrations. Seven-day treatment with nanomolar valinomycin concentrations caused a slight increase of the signal of the cationic fluorescent cyanine probe DiOC5(3) but did not appreciably affect adriamycin incorporation in the cells. A marked increase of the DiOC5(3) signal was obtained in the presence of micromolar valinomycin concentrations, which were incompatible with the in vitro cellular growth.

Carbocyanines↗
PubMed1991

Effects of polyene macrolides on the membrane potential of resting and activated human leukocytes.

Membrane potential changes in human polymorphonuclear leukocytes have been studied by monitoring the fluorescence signal of a carbocyanine probe in the presence of calcium ionophore A23187, chemotactic tripeptide f-met-leu-phe, and polyene macrolides. Reduction of the signals triggered by the ionophore and the tripeptide, inhibition of the respiratory burst, and changes in the Na+ influx into the cell seem to be the dominant effect of the polyenes. Polyene-induced depolarization does not correlate with the inhibition of the respiratory burst.

Amphotericin B↗
PubMed1990

Inhibition of erythrocyte ghost ATPase by polyene antibiotics.

The effect of micromolar concentrations of polyene antibiotics on erythrocyte ghost ATPase activities has been studied. (Mg2+)-ATPase is inhibited by amphotericin B and amphotericin B methyl ester, whereas (Na+ + K+ + Mg2+)-ATPase is inhibited by amphotericin B and lucensomycin. (Ca2+ + Mg2+)-ATPase is only slightly affected by polyene antibiotics.

Amphotericin B↗
PubMed1989

Combined effects exerted by amphotericin B and lucensomycin on cation permeability in a unilamellar vesicle system.

The permeability of artificial unilamellar vesicles and of plasma membrane vesicles from homogenized yeast in aqueous solutions of polyene antibiotics (amphotericin B and lucensomycin) was studied by measuring proton leakage by a pH-stat method. Micromolar concentrations of amphotericin B induced a remarkable proton efflux from the vesicles. Lucensomycin exerted similar effects only at 100 times higher concentrations. The latter antibiotic, at concentrations one order of magnitude lower than those necessary to induce a detectable proton efflux, seemed to protect the vesicles from the subsequent permeabilizing action of amphotericin B.

Amphotericin B↗
PubMed1989

Interaction of lucensomycin with membranes: the role of non-steroidal components.

The binding of lucensomycin to unilamellar phospholipid/cholesterol vesicles and to colloidal emulsions of cholesterol in aqueous solutions was studied by monitoring the changes in the electronic absorption spectra of the polyene antibiotic. The total extent of the absorption variations was a direct function of cholesterol concentration and quite independent of the nature of the emulsion. The rate of binding, relatively slow in the colloidal systems, was greatly enhanced when cholesterol was included in phospholipid-containing membranes. The rate of lucensomycin binding to colloidal cholesterol increased with increasing cholesterol concentrations and/or stirring the heterogeneous suspension. The time course of lucensomycin binding to vesicles appeared to be independent of the concentrations of phospholipids and cholesterol.

Antifungal Agents↗