Papers by Alfonso Pompella
Toxicological Sciences, 2019
Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as croc... more Asbestos is the main causative agent of malignant pleural mesothelioma. The variety known as crocidolite (blue asbestos) owns the highest pathogenic potential, due to the dimensions of its fibers as well as to its content of iron. The latter can in fact react with macrophage-derived hydrogen peroxide in the so called Fenton reaction, giving rise to highly reactive and mutagenic hydroxyl radical. On the other hand, hydroxyl radical can as well originate after thiol-dependent reduction of iron, a process capable of starting its redox cycling. Previous studies showed that glutathione (GSH) is one such thiol, and that cellular gamma-glutamyltransferase (GGT) can efficiently potentiate GSH-dependent iron redox cycling and consequent oxidative stress. As GGT is expressed in macrophages and is released upon their activation, the present study was aimed at verifying the hypothesis that GSH/GGT-dependent redox reactions may participate in the oxidative stress following the activation of macr...
Gamma-glutamyltransferase (GGT) is involved in glutathione (GSH) and S-nitrosoglutathione catabol... more Gamma-glutamyltransferase (GGT) is involved in glutathione (GSH) and S-nitrosoglutathione catabolisms, allowing the recovery of precursor aminoacids and nitric oxide release. Increased GGT serum levels were correlated with cardiovascular diseases, including atherosclerosis or hypertension, two contexts of vascular wall inflammation and oxidative stress [1]. However, less is known concerning vascular wall GGT activity under these contexts. GGT activity (L-γ-glutamyl-3-carboxy-4-nitroanilide) and intracellular GSH concentrations (2,3-naphthalenedicarboxaldehide) were evaluated in a rat smooth muscle cell line (SMC A-10) stimulated with lipopolysaccharide (LPS; 20 µg/mL, 24 h) or 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH; 50 mM, 2 h), and in aortas, from Spontaneously Hypertensive Rats (SHR) compared to normotensive Wistar Kyoto rats (WKY). The GGT activity increased in the inflammatory A-10 LPS model, while it decreased with oxidative stress, both in A-10 AAPH and SHR ao...
Materials Science and Engineering: C, 2021
The aim of this study was to evaluate the effectiveness of UVC photofunctionalization in removing... more The aim of this study was to evaluate the effectiveness of UVC photofunctionalization in removing the surface carbon contamination compounds from the most used surfaces utilized in dental implantology: TiO2, ZrO2 and PEEK. Machined samples were treated by UVC light in an Ushio Therabeam SuperOsseo® device for 12 min each. Non-treated disks were set as controls. X-Ray photoelectron spectroscopy was used to monitor the changes in surface chemical composition. Photofunctionalization of the PEEK material has been analyzed here for the first time. The removal of hydrocarbons allowed by UVC irradiation was nearly twofold, and irradiation simultaneously led to an increase of H-O-C=O bonds. For TiO2 and ZrO2 surfaces, the loss of hydrocarbons detected after UVC irradiation was threefold. The chemical stability of surfaces when left at atmospheric conditions after UVC irradiation was monitored during 10 weeks. After 6 weeks the carbon contamination on TiO2 surfaces returned to the level before UVC treatment, while for ZrO2 and PEEK it was 75% and 60% of its initial value, respectively. None of the materials tested displayed any toxicity towards human fibroblasts cultured in direct contact with them, confirming their potential employment for manufacturing of implant abutments. UVC photofunctionalization can be thus regarded as a valid method in order to reverse the detrimental effects of biological ageing of implant surfaces.
Journal of translational medicine, Jan 13, 2015
Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular ... more Gamma-glutamyltransferase (GGT) is a well-established independent risk factor for cardiovascular mortality related to atherosclerotic disease. Four GGT fractions have been identified in plasma, but only b-GGT fraction accumulates in atherosclerotic plaques, and correlates with other histological markers of vulnerability. The present study was aimed to evaluate whether macrophagic lineage cells may provide a source of b-GGT within the atherosclerotic plaque. GGT expression and release were studied in human monocytes isolated from peripheral blood of healthy donors. The growth factors GM-CSF and M-CSF were used to induce differentiation into M1-like and M2-like macrophages, respectively. Plaque GGT was investigated in tissue samples obtained from patients undergoing carotid endoarterectomy. We found that M1-like macrophages express higher levels of GGT as compared to M2-like, and that both monocytes and M1-like macrophages-but not M2-like-are able to release the b-GGT fraction upon ac...
Tumori Journal, 2003
ABSTRACT
Cancer Cell International, May 14, 2003
BACKGROUND: The molecular mechanisms by which iron is physiologically transported trough the cell... more BACKGROUND: The molecular mechanisms by which iron is physiologically transported trough the cellular membranes are still only partially understood. Several studies indicate that a reduction step of ferric iron to ferrous is necessary, both in the case of transferrin-mediated and transferrin-independent iron uptake. Recent studies from our laboratory described gamma-glutamyltransferase activity (GGT) as a factor capable to effect iron reduction in the cell microenvironment. GGT is located on the outer aspect of plasma membrane of most cell types, and is often expressed at high levels in malignant tumors and their metastases. The present study was aimed at verifying the possibility that GGT-mediated iron reduction may participate in the process of cellular iron uptake. RESULTS: Four distinct human tumor cell lines, exhibiting different levels of GGT activity, were studied. The uptake of transferrin-bound iron was investigated by using 55Fe-loaded transferrin, as well as by monitoring...
Previous work in our laboratory has shown that glutathione (GSH) availability is linked to cellul... more Previous work in our laboratory has shown that glutathione (GSH) availability is linked to cellular supply of ascorbic acid, through the action of γ-glutamyltransferase (GGT). This enzyme activity is expressed in bronchial epithelia, and is also secreted in epithelial lining fluid. We verified thus the possibility that GGT-mediated metabolism of glutathione may favour the supply of ascorbic acid to bronchial cells. Using human BEAS-2B cells transfected with GGT cDNA, as well as WT cells exposed to ELF-like GGT concentrations, we observed that indeed much higher (5–10 fold) levels of ascorbic acid are accumulated in the presence of GSH and active GGT. The data suggest that administration of aerosolized GSH to CF patients may as well concur to sustain the vitamin C status of bronchial epithelia. © 2007 Published by Elsevier B.V. on behalf of European Cystic Fibrosis Society.
The FASEB Journal, 2008
Objectives The objective of the current study was to investigate the prevalence rates of the foll... more Objectives The objective of the current study was to investigate the prevalence rates of the following infectious agents in 116 stray cats in the Barcelona area of Spain: Anaplasma phagocytophilum, Bartonella species, Borrelia burgdorferi, Chlamydia felis, Dirofilaria immitis, Ehrlichia species, feline calicivirus (FCV), feline herpesvirus-1 (FHV-1), feline leukaemia virus (FeLV), feline immunodeficiency virus (FIV), haemoplasmas, Mycoplasma species and Rickettsia species. Methods Serum antibodies were used to estimate the prevalence of exposure to A phagocytophilum, Bartonella species, B burgdorferi, Ehrlichia species and FIV; serum antigens were used to assess for infection by D immitis and FeLV; and molecular assays were used to amplify nucleic acids of Anaplasma species, Bartonella species, C felis, D immitis, Ehrlichia species, FCV, FHV-1, haemoplasmas, Mycoplasma species and Rickettsia species from blood and nasal or oral swabs. Results Of the 116 cats, 63 (54.3%) had evidence of infection by Bartonella species, FeLV, FIV or a haemoplasma. Anaplasma species, Ehrlichia species or Rickettsia species DNA was not amplified from these cats. A total of 18/116 cats (15.5%) were positive for FCV RNA (six cats), Mycoplasma species DNA (six cats), FHV-1 DNA (three cats) or C felis DNA (three cats). Conclusions and relevance This study documents that shelter cats in Catalonia are exposed to many infectious agents with clinical and zoonotic significance, and that flea control is indicated for cats in the region.
Frontiers in Pharmacology, 2020
The FASEB Journal, 1999
It has been reported in several cell lines that exposure to low levels of reactive oxygen species... more It has been reported in several cell lines that exposure to low levels of reactive oxygen species can exert a stimulatory effect on their proliferation. We have previously shown that mild oxidative conditions can also counteract apoptotic stimuli. A constitutive cellular production of low levels of superoxide and hydrogen peroxide originates from various sources; among these, g-glutamyl transpeptidase (GGT), the plasma membrane-bound activity in charge of metabolizing extracellular reduced glutathione, has recently been included. Since the inhibition of GGT is a sufficient stimulus for the induction of apoptosis in selected cell lines, we investigated whether this effect might result from the suppression of the mentioned GGT-dependent prooxidant reactions, on the theory that the latter may represent a basal antiapoptotic and proliferative signal for the cell. Experiments showed that: 1) GGT activity in U937 monoblastoid cells is associated with the production of low levels of hydrogen peroxide, and two independent GGT inhibitors cause a dose-dependent decrease of such GGT-dependent production of H 2 O 2 ; 2) GGT inhibition with acivicin results in cell growth arrest, and induces cell death and DNA fragmentation with the ladder appearance of apoptosis; 3) treatment of cells with catalase-and even more with Trolox C-is able to decrease their proliferative rate; 4) GGT inhibition (with suppression of H 2 O 2 production) results in a down-regulation of poly(ADP-ribose) polimerase (PARP) activity, which precedes the proteolytic cleavage of PARP molecule, such as that typically induced by caspases. The reported data suggest that the low H 2 O 2 levels originating as a by-product during GGT activity are able to act as sort of a 'life signal' in U937 cells, insofar as they can maintain cell proliferation and protect against apoptosis, possibly through an up-regulation of PARP activity.-Del Bello, B., Paolicchi, A., Comporti, M., Pompella, A., Maellaro, E. Hydrogen peroxide produced during g-glutamyl transpeptidase activity is involved in prevention of apoptosis and maintainance of proliferation in U937 cells.
Scientific Reports, 2017
Among the risk factors associated to metabolic syndrome (MetS), hypertension shows the highest pr... more Among the risk factors associated to metabolic syndrome (MetS), hypertension shows the highest prevalence in Italy. We investigated the relationship between the newly identified serum γ-glutamyltransferase (GGT) fractions, b-s-m-f-GGT, and risk factors associated to MetS in hypertensive patients. A total of ninety-five consecutive hypertensive patients were enrolled. GGT fractions were analysed by gel-filtration chromatography, and hepatic steatosis was evaluated by ultrasound. MetS was diagnosed in 36% of patients. Considering the whole group, band f-GGT showed the highest positive correlation with BMI, glucose, triglycerides and insulin, and the highest negative correlation with HDL cholesterol. While both serum triglycerides and insulin were independently associated with b-GGT levels, only triglycerides were independently associated with f-GGT. The values of b-GGT activity increased with steatosis grade (g0 = 1.19; g2 = 3.29; ratio g2/g0 = 2.75, p < 0.0001 linear trend). Patients with MetS showed higher levels of b-GGT, m-GGT and f-GGT [median (25 th-75 th) U/L
Biological chemistry, Jan 28, 2017
Decades of chemical, biochemical and pathophysiological research have established the relevance o... more Decades of chemical, biochemical and pathophysiological research have established the relevance of post-translational protein modifications induced by processes related to oxidative stress, with critical reflections on cellular signal transduction pathways. A great deal of the socalled 'redox regulation' of cell function is in fact mediated through reactions promoted by reactive oxygen and nitrogen species on more or less specific aminoacid residues in proteins, at various levels within the cell machinery. Modifications involving cysteine residues have received most attention, due to the critical roles they play in determining the structure/function correlates in proteins. The peculiar reactivity of these residues results in two major classes of modifications, with incorporation of NO moieties (S-nitrosation, leading to formation of protein S-nitrosothiols) or binding of low molecular weight thiols (Sthionylation, i.e. in particular S-glutathionylation, S-cysteinylglycinylat...
Colloids and surfaces. B, Biointerfaces, 2017
The use of zirconium oxide in dental implantology is rapidly increasing as it is regarded as bein... more The use of zirconium oxide in dental implantology is rapidly increasing as it is regarded as being more aesthetical and biologically friendly than titanium oxide. The interaction of titanium oxide with cells and proteins has proven to be significantly affected by the inevitable atmospheric hydrocarbon contamination, defined as biological ageing. The latter has proven to be effectively reversed by UVC irradiation. Crystal structures of both Zr and Ti oxides are very similar, thus also ZrO2 is prone to contamination by hydrocarbons. In the present study we have characterized the chemical-physical changes occurring to ZrO2 after UVC irradiation. Firstly a reduction by 3-fold of carbon present on its surface. XRD analysis has indicated that UVC irradiation treatment does not affect the crystalline structure of ZrO2, suggesting that it is possible to improve cell attachment on the surface without sacrificing the mechanical strength of the material. In addition a chemical model of interac...
Journal of Cystic Fibrosis, 2017
Frontiers in physiology, 2016
Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the ... more Aims: Gamma-glutamyl transferase (GGT), an enzyme present on the endothelium, is involved in the release of nitric oxide (NO) from S-nitrosoglutathione (GSNO) and in the GSNO-induced vasodilation. Endogenous GSNO is a physiological storage form of NO in tissues while exogenous GSNO is an interesting candidate for compensating for the decreased NO bioavailability occurring during cardiovascular diseases. We investigated in a rat model of human hypertension, the spontaneous hypertensive rat (SHR), submitted or not to high salt diet, whether a decreased vascular GGT activity modifies the vasorelaxant effect of GSNO. Methods: Thoracic aortic rings isolated from male SHR and Wistar Kyoto rats (WKY) aged 20-22 weeks-submitted or not for 8 weeks to a high salt diet (1% w/v NaCl in drinking water) were pre-constricted with phenylephrine then submitted to concentration-vasorelaxant response curves (maximal response: Emax; pD2) to carbachol or sodium nitroprusside to evaluate endothelial depe...
Journal of the Siena Academy of Sciences, 2016
Insect studies, dealing with parasitism of aphids, have shown that the disruption of host glutath... more Insect studies, dealing with parasitism of aphids, have shown that the disruption of host glutathione (GSH) pool and metabolisms significantly contributes to its physiological regulation and castration. The parasitic wasp <em>Aphidius ervi</em> injects into host aphids a venom containing large amounts of a gamma-glutamyltransferase (Ae-GGT) enzyme, which causes a depletion of GSH primarily involving ovarian tissue. Injected Ae-GGT in fact consumes substrate GSH, which ultimately triggers apoptosis. Studies on virulence factors of microrganisms have documented that the invasion strategies of selected pathogenic bacteria also target host GSH metabolism. Indeed, it has been shown that GGT activity of <em>Helicobacter pylori</em> and <em>H. suis</em>, the agents responsible of peptic ulcer, can exert antiproliferative and pro-apoptotic effects in gastric epithelial cells. By confocal microscopy, <em>H. suis</em> outer membrane vesicles (OM...
Curr Opin Pharmacol, 2007
PLOS ONE, 2016
Objectives To demonstrate that titanium implant surfaces as little as 4 weeks from production are... more Objectives To demonstrate that titanium implant surfaces as little as 4 weeks from production are contaminated by atmospheric hydrocarbons. This phenomenon, also known as biological ageing can be reversed by UVC irradiation technically known as photofunctionalization. To propose a new model from our experimental evidence to explain how the changes in chemical structure of the surface will affect the adsorption of amino acids on the titanium surface enhancing osteointegration.
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Papers by Alfonso Pompella