Citations of BMS244/3TEN
Peripheral Markers of Apoptosis in Parkinson's Disease. The Effect of Dopaminergic Drugs
BLANDINI,F.; MANGIAGALLI,A.; COSENTINO,M.; MARINO,F.; SAMUELE,A.; RASINI,E.; FANCELLU,R.; MARTIGNONI,E.; RIBOLDAZZI,G.; CALANDRELLA,D.; FRIGO,G.M.; NAPPI,G.
Annals of the New York Academy of Sciences 2003;1010:675-678.
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Abstract
Abstract: In this study, we measured the lymphocyte levels of proteins involved in apoptosis regulation, such as Bcl-2, the peripheral benzodiazepine receptor (PBR), caspase-3, and Cu/Zn superoxide dismutase (Cu/Zn SOD), in patients with Parkinson's disease (PD), either untreated or under therapy with dopaminergic agents (l-Dopa alone or l-dopa + dopamine agonists) and in healthy volunteers. All PD groups showed increased activity of caspase-3, compared to controls, particularly those under treatment only with l-Dopa. In this latter group, the increase in caspase-3 activity was also paralleled by an increase in the concentration of Cu/Zn SOD. In addition, patients taking l-Dopa + dopamine agonists showed marked decrease in Bcl-2 levels and increased PBR expression, which seems in keeping with the hypothesis that PBR may be functionally related to Bcl-2. In conclusion, we found clear modifications in the levels of proteins involved in the control of apoptosis in lymphocytes of PD patients. These changes were disease related but also modulated by the pharmacological treatment, which confirms the potential role of apoptosis in PD pathogenesis and the modulatory influence of dopaminergic agents
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Dopaminergic Modulation of Apoptosis in Human Peripheral Blood Mononuclear Cells. Possible Relevance for Parkinson's Disease
COLOMBO,C.R.I.S.; COSENTINO,M.A.R.C.; MARINO,F.R.A.N.; RASINI,E.M.A.N.; OSSOLA,M.A.R.I.; BLANDINI,F.A.B.I.; MANGIAGALLI,A.N.N.A.; SAMUELE,A.L.B.E.; FERRARI,M.A.R.C.; BOMBELLI,R.A.F.F.; LECCHINI,S.E.R.G.; NAPPI,G.I.U.S.; FRIGO,G.I.A.N.
Annals of the New York Academy of Sciences 2003;1010:679-682.
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Abstract
Abstract: Dopamine (DA) modulates apoptosis in neuronal and non-neuronal cells, and dopaminergic pathways contribute to neurodegenerative disease. Human lymphocytes express dopaminergic receptors and DA transporters, and synthesize endogenous catecholamines, which may modulate apoptosis in these cells. In the present study, dopaminergic modulation of apoptosis was investigated in human peripheral blood mononuclear cells (PBMCs) obtained from healthy donors. Twenty-four-hour DA reduced at 0.1-5 x 3 10-6 M and enhanced at 1-5 x 310-4 M spontaneous apoptosis. DA 1 x 310-6 M was inhibited by the D1-like receptor antagonist SCH 23390 1 x 310-6 M, but not by the D2-like receptor antagonists domperidone 1 x 3 10-6 M or haloperidol 1 x 3 10-6 M, while the effect of DA 5 x 3 10-4 M was prevented by the antioxidants glutathione 5-10 mM or N-acetyl-l-cysteine 1-10 mM. Intracellular reactive oxygen species were respectively reduced and increased by 1-3 h incubation with DA 0.1-10 x 3 10-6 M and 1-5x310-4 M. Twenty-four-hour DA 1 x 3 10-6 M or 5 x 3 10-4 M had no effect on PBMC expression of Cu/Zn superoxide dismutase or Bcl-2; however, DA 5 x 3 10-4 M decreased caspase-3 activity. In human PBMCs, DA seems to promote apoptosis through oxidative mechanisms but may also result in cell rescue from apoptotic death possibly through activation of D1-like receptors. The dual effect of DA on human PBMCs closely resembles that on striatal neurons. Lymphocytes of patients with Parkinson's disease may show reduced DA content and impaired DA transporter immunoreactivity. Human PBMCs may thus represent a simple and readily accessible model to study DA-related mechanisms relevant for neurodegenerative disease
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Effects of homocysteine on apoptosis-related proteins and anti-oxidant systems in isolated human lymphocytes
Mangiagalli,Anna; Samuele,Alberta; Armentero,Marie Therese; Bazzini,Eleonora; Nappi,Giuseppe; Blandini,Fabio
European Journal of Biochemistry 2004;271:1671-1676.
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Abstract
Homocysteine (Hcy) is a nonprotein-forming sulphur amino acid that plays an important role in remethylation and trans-sulphuration processes. In recent years, it has been suggested that increased levels of plasma Hcy may play a role in the pathogenesis of various diseases, particularly at the cardiovascular level. The pathogenic mechanism of hyperhomocysteinemia, however, has not been clarified. Because oxygen radicals can be generated by the auto-oxidation of this amino acid, it has been suggested that Hcy may cause cellular damage through oxidative mechanisms, ultimately leading to apoptotic cell death. In this study, we sought to investigate the effects of Hcy on oxidative damage and antioxidant agent levels, as well as on apoptosis-related proteins and apoptosis occurrence in human cells. For this purpose, we measured levels of Bcl-2, caspase-3 and caspase-9 activity, Cu/Zn superoxide dismutase, reduced glutathione, lipid peroxidation [malondialdehyde and 4-hydroxy-2 (E)-nonenal concentrations], apoptotic single-stranded DNA and nuclear changes in human isolated lymphocytes exposed to increasing concentrations of Hcy. Incubation with Hcy did not induce significant changes in any of these biomarkers. Therefore, our results do not support the existence of a direct link between increased levels of Hcy and the occurrence of a pro-apoptotic state mediated by enhanced oxidative stress
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Intermittent High Glucose Enhances Apoptosis Related to Oxidative Stress in Human Umbilical Vein Endothelial Cells: The Role of Protein Kinase C and NAD(P)H-Oxidase Activation
Quagliaro,Lisa; Piconi,Ludovica; Assaloni,Roberta; Martinelli,Lucia; Motz,Enrico; Ceriello,Antonio
Diabetes 2003;52:2795-2804.
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Abstract
The effects of intermittent and constant high glucose in the formation of nitrotyrosine and 8-hydroxydeoxyguanosine (markers of oxidative stress), as well as the possible linkage between oxidative stress and apoptosis in endothelial cells, have been evaluated. Stable high glucose increased nitrotyrosine, 8-hydroxydeoxyguanosine (8-OHdG), and apoptosis levels. However, these effects were more pronounced in intermittent high glucose. Protein kinase C (PKC) was elevated in both such conditions, particularly in intermittent glucose. The adding of the PKC inhibitors bisindolylmaleimide-I and LY379196, a specific inhibitor of PKC-{beta} isoforms, normalized nitrotyrosine and reduced 8-OHdG concentration and cell apoptosis in both stable and intermittent high glucose. Similar results were obtained with the MnSOD mimetic Mn(III)tetrakis(4-benzoic acid)porphyrin chloride that normalized nitrotyrosine, 8-OHdG, and apoptosis and inhibited PKC activation. NAD(P)H oxidase was also measured. NAD(P)H oxidase components p47phox, p67phox, and p22phox was overexpressed during both stable and intermittent high glucose. PKC inhibition and MnSOD mimetic normalized this phenomenon. In conclusion, our study shows that the exposure of endothelial cells to both stable and intermittent high glucose stimulates reactive oxygen species overproduction also through PKC-dependent activation of NAD(P)H oxidase, leading to increased cellular apoptosis. Our data suggest that glucose fluctuations may also be involved in the development of vascular injury in diabetes
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Analysis of resveratrol-induced apoptosis in human B-cell chronic leukaemia
Roman,Viviana; Billard,Christian; Kern,Catherine; Ferry-Dumazet,Helene; Izard,Jean Claude; Mohammad,Ramzi; Mossalayi,Djavad M.; Kolb,Jean Pierre
British Journal of Haematology 2002;117:842-851.
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Abstract
Summary. Trans-resveratrol was analysed for its apoptotic and growth inhibitory activity in human B-cell lines derived from chronic B-cell malignancies (WSU-CLL and ESKOL), and in leukaemic lymphocytes from patients with B-cell chronic lymphocytic leukaemia (B-CLL). Resveratrol displayed antiproliferative activity on both B-cell lines, as estimated by the decrease in cell recovery and inhibition of thymidine uptake. Furthermore, resveratrol induced apoptosis in the two cell lines as well as in B-CLL patients' cells, as evidenced by the increase in annexin V binding, caspase activation, DNA fragmentation and decrease of the mitochondrial transmembrane potential DeltaPsim. We previously reported that nitric oxide (NO), endogenously released by an iNO synthase (iNOS) spontaneously expressed in these leukaemic cells, contributed to their resistance towards apoptosis. We show here that resveratrol inhibited both iNOS protein expression and in situ NO release in WSU-CLL, ESKOL and B-CLL patients'cells. In addition, Bcl-2 expression was also inhibited by resveratrol. Thus, downregulation of the two anti-apoptotic proteins iNOS and Bcl-2 can contribute to the apoptotic effects of resveratrol in leukaemic B cells from chronic leukaemia. Our data suggest that this drug is of potential interest for the therapy of B-CLL
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