A Antonucci

Università degli Studi G. d'Annunzio Chieti e Pescara, Chieta, Abruzzo, Italy

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Publications (101)171.12 Total impact

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    A Cataldi · S Zara · M Rapino · M Zingariello · V di Giacomo · A Antonucci
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    ABSTRACT: Cellular senescence implies loss of proliferative and tissue regenerative capability. Also hypoxia, producing Reactive Oxygen Species (ROS), can damage cellular components through the oxidation of DNA, proteins and lipids, thus influencing the shortening of telomeres. Since ribonucleoprotein Telomerase (TERT), catalyzing the replication of the ends of eukaryotic chromosomes, promotes cardiac muscle cell proliferation, hypertrophy and survival, here we investigated its role in the events regulating apoptosis occurrence and life span in hearts deriving from young and old rats exposed to hypoxia. TUNEL (terminal-deoxinucleotidyl -transferase- mediated dUTP nick end-labeling) analysis reveals an increased apoptotic cell number in both samples after hypoxia exposure, mainly in the young with respect to the old. TERT expression lowers either in the hypoxic young, either in the old in both experimental conditions, with respect to the normoxic young. These events are paralleled by p53 and HIF-1 α expression dramatic increase and by p53/ HIF-1 α co-immunoprecipitation in the hypoxic young, evidencing the young subject as the most stressed by such challenge. These effects could be explained by induction of damage to genomic DNA by ROS that accelerates cell senescence through p53 activation. Moreover, by preventing TERT enzyme down-regulation, cell cycle exit and apoptosis occurrence could be delayed and new possibilities for intervention against cell ageing and hypoxia could be opened.
    Preview · Article · Dec 2009 · European journal of histochemistry: EJH
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    ABSTRACT: Nuclear speckles, which are sites of pre-mRNA splicing and/or assembly components, are diffusely distributed throughout the nucleoplasm. They are composed of splicing factors (SFs), including SC-35, which are nuclear proteins that remove introns (noncoding sequences in the genes) from precursor mRNA molecules, to form mature RNA, which will be transported to the cytoplasm, site of protein synthesis and activation. In light of such evidences, here we report that hypoxia modulates in vivo SC-35 SF phosphorylation via protein kinase C (PKC) delta in young rat heart. Trichrome Mallory staining and TUNEL analysis along with immunohistochemistry and Western blotting have been performed on left ventricles excised from young and old rats exposed to intermittent hypoxia. Although young hypoxic myocardial cells appear smaller than normoxic cells, connective and endothelial components increase, SC-35 phosphorylation is particularly evident in the endothelium and paralleled by an increased expression of vascular endothelial growth factor (VEGF). In addition, SC-35 and PKC delta coimmunoprecipitation occurs, suggesting that SC-35 phosphorylation could be PKC delta-mediated and that hypoxic young heart needs to counteract the damage through a process of neoangiogenesis involving such SF. Even though the levels of SC-35 and PKC delta are high, the similar response disclosed by normoxic and hypoxic old rat hearts (both showing a fibrotic organization, similar endothelial components and VEGF levels) could be due to the existence of an impaired oxygen sensing mechanism and thus to a low rate of angiogenesis.
    Full-text · Article · Aug 2009 · The Anatomical Record Advances in Integrative Anatomy and Evolutionary Biology
  • S Zara · D Bosco · C Di Giulio · A Antonucci · A Cataldi
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    ABSTRACT: Rat myocardial fiber development and formation is a complex event which begins in the early stages of fetal life and continues until the end of the first month of life. In fact, a progressive morphological structure arrangement is observed until the 22nd day of life. These modifications are based on biochemical events which are switched on at plasma membrane level and then transduced into the nucleus. Since the presence of Protein Kinase C (PKC) inside the nucleus could allow the enzyme to phosphorylate also proteins located on chromatin, on nuclear matrix and speckles, in this study attention was paid to the role played by phospho-Protein Kinase C-alpha (p-PKCalpha) in regulating the activation of SC-35 splicing factor which leads to the occurrence of morphological modifications during post-natal rat heart development. Besides the parallel increase of the expression of both proteins up to 4/8 days of life, firstly p-PKCalpha and SC-35 co-localize at nuclear level at day 1 after birth, thus suggesting a main role of p-PKCalpha in modulating the early transcription of components related to post-natal rat heart development.
    No preview · Article · Jan 2009 · Journal of biological regulators and homeostatic agents
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    ABSTRACT: We examined lymphocyte apoptosis, activity of caspases-1, -3, -8 and -9 and the relationship between those two events and inflammation response in septic shock. Blood samples were obtained within 24 h after diagnosis of septic shock from 16 patients to measure apoptosis, caspases-3, -8, -9 expression, changes in mitochondrial transmembrane potential and expression of Fas/FasL system of peripheral blood mononuclear cells (PBMCs). Moreover, serum levels of caspase-1 and blood concentrations of IL-6, IL-12, IL-15 and IL-18 were assessed. PBMCs from patients with septic shock compared to control individuals exhibited a greatly increased frequency of apoptosis (39.10 +/- 7.33% vs 4.19 +/- 1.13%; p < 0.001), an over expression of caspases-3, -8, and -9 (p < 0.01, p < 0.05, p < 0.001 for caspases-3, -8 and -9, respectively) as well as of Fas/FasL system (p < 0.05) and significant changes in mitochondrial transmembrane potential. Blood levels of caspase-1 (101.5 +/- 18.2 pg/ml vs 9.09 +/- 2.7 pg/ml, p < 0.001) and of IL-6, IL-12, IL-15 and IL-18 were significantly higher in septic patients vs control (p < 0.0001, p < 0.05, p < 0.05 and p < 0.0001, respectively). Furthermore, a correlation linking IL-6 blood level with both the apoptotic rate (r(2) = 0.75; p = 0.001) and caspase-9 expression (r(2) = 0.92; p = 0.0001) of PBMCs was observed.
    Full-text · Article · Oct 2008 · Infection
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    ABSTRACT: Both hypoxia and aging affect the morphology and the function of rat myocardial tissue. Moreover the heart tries to counteract the impaired function by activating specific signalling cascades. Here we report the involvement of CREB protein in "in vivo" response to hypoxic challenge and during aging in rat hearts. CREB is activated in parallel to HIF-1alpha nuclear translocation in the young after hypoxia exposure followed by reoxygenation, while this kind of response is not so dramatic in the old, neither in terms of CREB activation, neither in terms of HIF-1alpha expression and translocation, suggesting in the old the existence of an impaired oxygen-sensing mechanism or an adaptation of the cells to hypoxia. Moreover in the young a PKC alpha/Erk pathway seems to be involved in the activation of HIF-1alpha along with CREB, suggesting an attempt of the young to counteract the damage evoked by hypoxia, while in the old a PKC alpha/p38 MAPK/CREB pathway could determine the occurrence of both aging and aged cell hypoxia response.
    No preview · Article · Apr 2007 · Histochemie
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    N M Maraldi · G Mazzotti · R Rana · A Antonucci · R Di Primio · L Guidotti
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    ABSTRACT: Here we present an overview of the experimental evidence and of the conceptual basis for the involvement of lamins and nuclear envelope proteins in a group of genetic diseases collectively referred to as laminopathies. Some of these diseases affect a specific tissue (skeletal and/or cardiac muscles, subcutaneous fat, peripheral nerves), while others affect a variety of tissues; this suggests that the pathogenic mechanism of laminopathies could reside in the alteration of basic mechanisms affecting gene expression. On the other hand, a common feature of cells from laminopathic patients is represented by nuclear shape alterations and heterochromatin rearrangements. The definition of the role of lamins in the fine regulation of heterochromatin organization may help understanding not only the pathogenic mechanism of laminopathies but also the molecular basis of cell differentiation and ageng.
    Preview · Article · Feb 2007 · European journal of histochemistry: EJH
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    ABSTRACT: During development and aging, as well as under hypoxia, many cells can adapt to a stressful environment, while others are damaged and die by apoptosis. In particular, intermittent hypoxia, i.e., hypoxia followed by reoxygenation, determines different responses in young and adult myocardia. In the rat myocardium exposed to hypoxia, the roles played by p53 and p66 Shc proteins in matching, in an age-dependent mode, in stabilizing hypoxia-inducible factor-1alpha (HIF-1alpha), and in preventing its biological activity, which usually induces synthesis of rescue proteins against this stress, were investigated. Five animals from three groups, each consisting of 10 male Wistar rats, 8 days and 3 and 24 months old, were kept under physiological conditions; 5 young and 5 old rats were exposed to intermittent hypoxic challenges (12 h at 10% O2 followed by 12 h at 21% O2) for 8 days. Pregnant rats were kept for 3 days under hypoxic conditions before delivery, and 5 neonate rats were kept in intermittent hypoxia for 8 days. Left ventricles were excised and processed for TUNEL and Western blotting analyses. HIF-1alpha stabilization by p53 along with decline in Bcl2, substantial caspase-3 expression, and a large number of apoptotic events make the hypoxic young myocardium the most damaged when compared to the neonatal one, in which HIF-1alpha is not stabilized. Moreover, high expression and activation of p66 in hypoxic young and in normoxic old myocardia suggests a pathological increase of the response to oxidative stress in the former and a physiological progressive increase in the latter. The different responses to hypoxic challenge during life show that the young seem the most reactive and damaged, as is well documented by p53-mediated HIF-1alpha stabilization. The neonate, not showing any modification in terms of HIF-1alpha expression and activation, seems 'adapted' to such an environment, since it was maintained in hypoxia 3 days before and 8 days after birth. In the old, increasing p66 expression and tyrosine phosphorylation, probably exerting a slight HIF-1alpha stabilization in the two experimental conditions, provide evidence of longevity and oxidative stress resistance, as suggested by the low number of apoptotic events seen upon hypoxic challenge, and this fact could be due to impairment of oxygen-sensing mechanisms or to adaptation of the cells to apoptosis.
    No preview · Article · Feb 2006 · Gerontology
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    ABSTRACT: Intermittent hypoxia, followed by reoxygenation, determines the production of reactive oxygen species (ROS), which may lead to accelerated aging and to the appearance of age-related diseases. The rise in ROS levels might constitute a stress-stimulus activating specific redox-sensitive signalling pathways, so inducing either damaging or protective functions. Here, we report that in old rat cerebral cortex exposed to hypoxia, the accumulation in the cytoplasm of hypoxic inducible factor 1alpha (HIF-1alpha)--the master regulator of oxygen homeostasis--concomitant with p66(Shc) activation and reduced IkBalpha phosphorylation is associated with tissue apoptosis or necrosis. In young cerebral cortex, we hypothesize that the hypoxic damage may be reversible, based on our demonstration of elevated HIF-1alpha levels, combined with a low level of IkBalpha phosphorylation, a decrease in IAP-1 and a lack of major change in Bcl2 family proteins. These observations are associated with a low level of cell death induced by hypoxia, suggesting that HIF-1alpha activation in cortical neurons may produce rescue proteins in response to intermittent hypoxia.
    Full-text · Article · Sep 2005 · Aging Cell
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    G Delogu · A Antonucci · M Signore · M Marandola · G Tellan · F Ippoliti
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    ABSTRACT: An alteration in production of both interleukin-10 (IL-10) and nitric oxide (NO) has been found following surgical/anaesthesia trauma. It is also suggested that IL-10 could be an important factor in regulating NO metabolism during the postoperative period. Furthermore, NO seems to play a crucial role in the anaesthetic state. The purpose of this study was to investigate plasma levels of IL-10 and NO following surgery, any possible correlation between these two variables and whether anaesthesia technique could influence NO and IL-10 circulating concentrations. Thirty-two patients scheduled to undergo elective major surgery were enrolled in the study and allocated into two groups to receive two different techniques of anaesthesia, total intravenous (i.v.) anaesthesia (Group I) and inhalational anaesthesia (Group II). Blood samples were drawn before (t0), at the end (t1) of operation and after 24 h (t2). Plasma IL-10 and NO levels were measured by using an enzyme-linked-immunosorbent assay (ELISA) and a total NO assay kit, respectively. In both patient groups there was a significant decrease of plasma NO levels at the end of surgery (30.35 +/- 2.70 mmol L(-1) at t0 to 13.76 +/- 1.51 mmol L(-1) at t1 in Group I, P < 0.0001; 28.23 +/- 2.50 mmol L(-1) at t0 to 11.38 +/- 0.95 mmol L(-1) at t1 in Group II, P < 0.0001). This reduction remained at 24 h postoperatively (14.33 +/- 1.52 mmol L(-1) in Group I, P < 0.0001; 12.52 +/- 1.11 mmol L(-1) in Group II, P < 0.0001, both vs. t0). There was an increase in IL-10 concentrations (26.35 +/- 3.42 pg mL(-1) and 75.39 +/- 8.33 pg mL(-1) at t1 and t2, respectively, vs. 4.93 +/- 0.31 pg mL(-1) at t0, P = 0.03 and P < 0.0001, respectively, in Group I; 26.18 +/- 3.22 pg mL(-1) and 69.91 +/- 7.33 pg mL(-1) at t1 and t2, respectively, vs. 5.50 +/- 0.33 pg mL(-1) at t0, P = 0.02 and P < 0.0001, respectively, in Group II). No relationship was found between circulating IL-10 and NO. During the postoperative period, IL-10 overproduction does not correlate with the decrease in systemic NO concentration.
    Full-text · Article · Jun 2005 · European Journal of Anaesthesiology
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    ABSTRACT: During heart development, cell hyperplasia and hypertrophy are the main mechanisms by which cardiac mass grows. Both these processes along with programmed cell death lead to complete growth and function. In addition, since the establishment of cardiac function depends on the relationship between oxygen supply and demand, we investigated some of the molecular mechanisms at the basis of rat myocardial cell response to hypoxic stress at different times of neonatal life. In particular, the role played by hypertrophic and survival factors like NF-kB and IAP-1 (Inhibiting Apoptosis Protein) and by death factors ASK-1 (Apoptosis Signal Regulating Kinase), JNK/SAPK (Jun-N-Terminal-Kinase/Stress-Activated Protein Kinase) pathways in regulating caspase-3 expression and activity has been evaluated by immunohistochemical and Western blotting analyses, respectively. Level of phosphorylation of IkBalpha and IAP-1 expression were substantial in 8-day-old hypoxic hearts, suggesting the persistence of NF-kB driven hypertrophic signal along with a rescue attempt against hypoxic stress. In contrast, ASK-1 mediated JNK/SAPK activation, regulating Bcl(2) levels, allows Bax homodimerization and caspase-3 activation in the same experimental conditions. Thus, a regulation carried out by NF-kB and JNK/SAPK pathways on caspase-3 activation at day 8 of neonatal life can be suggested as the main factor for the heart 'adaptive' response to hypoxia.
    No preview · Article · Apr 2005 · Journal of Molecular Histology
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    M Marandola · A Antonucci · G Tellan · A Fegiz · R Fazio · S Scicchitano · G Delogu
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    ABSTRACT: The aim of the study was to determine whether intrathecal sufentanil alone provides an adequate analgesia for patients undergoing transurethral resection of the bladder (TURB) and to compare it to standard spinal bupivacaine anesthesia in terms of motor and sensory blockade, discharge time and side effects. Sixty-two patients were blindly and randomly assigned to receive either intrathecal bupivacaine (10 mg of 0.5% hyperbaric bupivacaine) or intrathecal sufentanil (15 microg). Motor and sensory blockade was evaluated using a modified Bromage scale as well as cold and pinprick tests. Severity of pain was assessed by means of a 10-point verbal analog scale. We found that the mean duration of sensory blockade was similar for both sufentanil and bupivacaine patients but the quality of analgesia induced by sufentanil alone was poor as compared with spinal bupivacaine anesthesia. The subarachnoid administration of sufentanil 15 mg seems to be inadequate for TURB surgery. In addition, the advantage of a faster recovery we observed in sufentanil patients is minimized by the occurrence of a troublesome symptom such as pruritus. On the other hand, spinal bupivacaine produces an undesirable motor blockade exceeding, in our opinion, the requirement for TURB procedure.
    Full-text · Article · Apr 2005 · Minerva anestesiologica
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    ABSTRACT: The development and growth of the rat heart implies hyperplasia, which stops at birth, and hypertrophy, allowing cardiac mass to grow in response to programmed genetic events along with to haemodynamic overload. Moreover, hypertrophy is accomplished to apoptosis which controls the final number of myocardial cells, deletes vestigial structures, and takes part in remodelling the organ. Since at the basis of all these processes, which lead to the complete development of the heart, the activation of specific signalling pathways underlies, attention has been addressed to the role played in vivo by Protein Kinase C zeta (PKC zeta) in regulating NF-kB signalling system and intrinsic mitochondrial apoptotic route at days 1, 4, 10 and 22 of rat life. In fact, a role has been assigned to PKC zeta in indirectly phosphorylating IKBa, which peaks between 10 and 22 days, through a IKK determining, in turn, NF-kB activation, concomitantly to cytochrome c/Apaf 1 co-localization in the cytoplasm and caspase-9/caspase-3 activation, which leads to the occurrence of apoptosis. Thus a key role for PKC zeta in regulating the hypertrophic and apoptotic events leading to establishment of complete function in rat neonatal heart is here suggested.
    No preview · Article · Jan 2005 · International journal of immunopathology and pharmacology
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    ABSTRACT: Genomic instability is recognized as a cause of cellular apoptosis and certain drugs that exhibit a proapoptotic effect are also able to induce chromosome damage. Since we found in recent experiments that drugs such as pancuronium and fentanyl exerted an apoptogenic effect on T cells, we studied the capacity of those agents to promote chromosome instability, i.e. chromosome aberrations (CA) and telomeric associations (tas) in peripheral blood lymphocytes. Lymphocytes from healthy donors were cultured with pancuronium or fentanyl, using two different concentrations for each drug: 20 and 200 ng/ml for pancuronium and 10 and 30 ng/ml for fentanyl, respectively. Cells were exposed to each concentration of these drugs either for 24 or 48 h. The higher concentration chosen was the same at which we detected the proapoptotic effect in our previous works. Cytogenetic analysis was performed by means of a standard technique and chromosome aberrations or telomeric associations were blindly evaluated by two independent observers. The chromosome aberrations we observed in treated cells were not significantly different from control lymphocytes. However, an unusual rate of telomeric associations (P < 0.001) was detected in cells exposed to both pancuronium and fentanyl, at each concentration tested and at each exposure time of the study. Fentanyl and pancuronium do not have a direct clastogenic effect on T cultures, but at the same concentrations at which we demonstrated their apoptogenic power, these drugs are able to increase genomic instability through inducing an elevated rate of telomeric associations. Such a capacity could exploit in peripheral T cells the same mitochondrion-mediated signal pathway of apoptosis death.
    Full-text · Article · Sep 2004 · Acta Anaesthesiologica Scandinavica
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    Full-text · Article · Jun 2004 · European Journal of Anaesthesiology
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    ABSTRACT: Exposure of rats to intermittent hypoxia determines different responses at tissue and cell level. Heart mainly undergoes the effects of hypoxic injury and its response is determined both by the relationship between oxygen supply and demand and by its functional state. Since molecular mechanisms mediate cells sensing and response to low O(2) concentration, here we explore the role played by Protein Kinase C alpha (PKC alpha) in the signal transduction mechanisms leading to the occurrence of morphological responses in rat neonatal, young and old heart subjected to intermittent hypoxia. Along with a key role for hypoxia inducible factor and vascular endothelial growth factor in the occurrence of continuous state of dynamic adaptation of vasculature, PKC alpha presumably phosphorylates IkBalpha in rat normoxic and hypoxic neonatal hearts, supporting the hypothesis of a rescue strategy carried out against hypoxia, together with an hypertrophic response. In hypoxic young heart PKC alpha activation, paralleled by sustained Bax homodimerization and caspase-3 activation, along with reduced p-IKBalpha and Inhibiting Apoptosis Protein (IAP) expression, suggests that the young early and deeply undergoes the effects of lowered oxygen tension. In addition, since no modifications concerning PKC alpha driven signalling system are evidenced in both the experimental conditions, we suggest an oxygen impaired sensing during ageing.
    No preview · Article · Apr 2004 · Experimental Gerontology
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    ABSTRACT: Several compounds used in anesthesia practice have demonstrated to impair immune function and to influence the process of apoptotic death in T cell population following surgical trauma. We designed this study to test in vitro the impact of neuromuscular blocker, such as pancuronium, at clinically relevant concentration on lymphocyte apoptosis, death factor expression and mitochondrial function. Following isolation, lymphocytes were incubated with pancuronium bromide at a clinically relevant concentration (0.136 micro mol l-1) for 3 h at 37 C in a 5% carbon-dioxide-humidified atmosphere and the frequency of apoptotic lymphocytes was then measured. We also investigated crucial steps in the apoptotic process, including Fas/Fas ligand (FasL) phenotype, intracellular expression of the interleukin-1beta-converting enzyme (ICE) p20, mitochondrial membrane potential (DeltaPsim), generation of mitochondrial reactive oxygen species, and glutathione (GSH) levels. Control experiments were performed incubating cells in the complete culture medium added with the dilution medium of the drug without addition of the drug. Expression of Fas, FasL and ICEp20 was six-fold, four-fold, and five-fold increased, respectively, among pancuronium-treated lymphocytes with respect to control cultures (P = 0.0001). The percentage of cells exhibiting either dissipation of mitochondrial membrane potential or increased production of reactive oxygen species was seven-fold increased following exposure to pancuronium compared with untreated lymphocytes (P = 0.0001). These findings were associated with a decrease in GSH level. In addition, the frequency of apoptotic cells was 10-fold greater among lymphocytes cultured in the presence of the drug with respect to control cultures. (P = 0.0001). Our data suggest an apoptogenic effect of pancuronium in vitro at clinically relevant concentration on peripheral blood lymphocytes. This could be implicated in the transient immune suppression following a surgical operation.
    Full-text · Article · Nov 2003 · Acta Anaesthesiologica Scandinavica
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    ABSTRACT: From birth to aging the heart undergoes functional changes reflecting biochemical and ultrastructural modifications which imply apoptosis. This is a physiological process resulting from genetic programs closely associated with development and aging. During development apoptosis eliminates redundant cells leading to heart remodeling, while during aging it eliminates damaged or exhausted cells. In the present paper we analyze some molecular mechanisms involved with heart morphological modifications, especially in the neonatal heart which displays different features in the subendocardial and myocardial area. The high number of subendocardial apoptotic cells and the inverted ratio of Bcl-2/Bax molecule expression in the two heart compartments led us to hypothesize a different metabolism in the myocardium as compared with subendocardium. Moreover, we propose that PKC zeta may mediate this different response by activating Nf-kB pathway and by maintaining the balance between hypertrophic growth and apoptosis involved with remodeling of neonatal heart. Further, we underline that in the aged heart, where this pathway is not activated, such balance is not maintained.
    No preview · Article · Aug 2003 · Mechanisms of Ageing and Development
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    ABSTRACT: During ageing, the occurrence of apoptosis is due to a progressive impairment of normal functions, leading to eliminate redundant, damaged or infected cells. Here we report that also in myocardial tissue, ageing, besides reduction of the number of myocytes and of specialized conduction tissue cells, reduction in Ca(++) transport across the membrane, includes the establishment of apoptosis. In particular, the occurrence of this process, which is less represented than we would have expected, is mediated by the balance between the well known Bcl-2 protein family members, Bad, Bax and Bcl-2, related to the pathway PI-3-kinase/AKT-1, which is known to deliver a survival signal. In fact, aged myocardial cells disclose a suboptimal response, which underlines the possibility that they can become more sensitive to damaging factors or diseases, more frequently occurring during ageing, probably due to an exploited molecular control of apoptosis.
    No preview · Article · Mar 2002 · Mechanisms of Ageing and Development
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    ABSTRACT: Previous studies have shown that a profound suppression of immune function transiently occurs in patients who undergo surgery under general anesthesia. The decline in the absolute counts of peripheral blood lymphocytes constitutes a major factor accounting for this immune defect, and recent evidence indicates that apoptosis plays a crucial role in determining postsurgical lymphocytopenia. An altered oxidation-reduction status of mitochondria may contribute through apoptosis to the loss of lymphocytes following surgical trauma and general anesthesia. We studied 16 patients with American Society of Anesthesiologists' physical status I or II who underwent elective surgery under general anesthesia. The data were collected prospectively. University hospital. Samples of peripheral blood were drawn on the day before surgery and at 24 and 96 hours after the operation. Following lymphocyte isolation, the mitochondrial transmembrane potential was assessed by flow cytometry using 3,3'-dihexylocarbo-cyanine iodide, and stains with hydroethidine and 2'-7'-dichlorofluorescein diacetate were used to determine the generation of reactive oxygen species. The labeling of lymphocytes with monobromobimane was used to assess the presence of reduced glutathione. At 24 hours after surgery, we detected a significantly elevated frequency of peripheral blood lymphocytes (P =.002), which incorporated low levels of 3,3'-dihexylocarbo-cyanine iodide, compared with the preoperative period. At this same time point, the frequency of lymphocytes with the hydroethidine- and 2'-7'-dichlorofluorescein diacetate-positive phenotype was elevated compared with baseline levels. Conversely, at 24 hours after surgery, the frequency of cells that stained positive for glutathione was strongly decreased compared with preoperative values. Overall measurements returned to the baseline levels at 96 hours after surgery. The strict association we observed between the overproduction of reactive oxygen species and the disruption of the mitochondrial transmembrane potential supports the view that alterations in mitochondrial energy metabolism, paralleled by the presence of a pro-oxidant oxidation-reduction status, could be involved in the accelerated apoptotic loss of lymphocytes following surgical trauma and general anesthesia.
    No preview · Article · Nov 2001 · Archives of Surgery
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    ABSTRACT: The expression, cellular distribution, and activity of PIP(2)-specific phospholipase C (PLC) in healthy human gastric-mucosa cells have been recently studied in our laboratories and a direct evidence for an almost exclusive expression of PLC beta isoforms, with the exception of PLC beta4, has been provided. These results addressed our attention to possible modification of PLC expression and activity during neoplastic transformation of the human gastric mucosa. In the present article we present results indicating that PLC delta2 is markedly expressed in type II intestinal metaplasia and in the adenocarcinoma whereas traces of other PLC isoforms were sometime detected. Interestingly, we found that type I intestinal metaplasia was in the majority of the cases PLC delta2-negative, but when expressed, this type of metaplasia generally considered as benignant, always evolved toward neoplastic transformation. These results therefore readdress the question of surveillance of the patients with type I intestinal metaplasia and suggest that PLC delta2 expression might be a possible marker of gastric malignant transformation.
    Full-text · Article · Oct 2001 · American Journal Of Pathology

Publication Stats

824 Citations
171.12 Total Impact Points

Institutions

  • 1989-2009
    • Università degli Studi G. d'Annunzio Chieti e Pescara
      • Dipartimento di Scienze Biomediche
      Chieta, Abruzzo, Italy
    • Università degli Studi di Urbino "Carlo Bo"
      Urbino, The Marches, Italy
  • 2005
    • Umberto I Policlinico di Roma
      Roma, Latium, Italy
  • 1988-2001
    • Sapienza University of Rome
      • • Department of Experimental Medicine
      • • Department of Surgical Sciences
      • • Department of Biochemical Sciences "Alessandro Rossi Fanelli
      Roma, Latium, Italy
  • 1994
    • Polo d'Innovazione di Genomica Genetica e Biologia
      Perugia, Umbria, Italy
  • 1975-1983
    • The American University of Rome
      Roma, Latium, Italy
  • 1976
    • Università Degli Studi Roma Tre
      Roma, Latium, Italy