194 results on '"Condorelli, DF"'
Search Results
2. Identification and functional binding analysis of GPR23/! LPA4 as a candidate G protein-coupled receptor for Guanosine
- Author
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GRILLO, Maria, DI LIBERTO, Valentina, MUDO', Giuseppa, BELLUARDO, Natale, GAROZZO, R, CACIAGLI, F, CONDORELLI, DF, GRILLO, M, DI LIBERTO, V, GAROZZO, R, MUDÒ, G, CACIAGLI, F, CONDORELLI, DF, and BELLUARDO, N
- Subjects
Binding assay ,Guanosine ,Brain ,Gpr23 ,Settore BIO/09 - Fisiologia - Abstract
Several studies have shown that guanine-based purines exert biological effects on the central nervous system (CNS), possibly through membrane receptors, but at the present there are not reports related to the identification of such specific receptor(s). We have identified the first guanosine G protein-coupled receptor GPR23, also known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell line (U87). We report that the silencing of GPR23 reduces significantly the antiproliferative effects of guanosine, while stably transfected cell clones over-expressing GPR23 increase sensitivity to guanosine. [3H] Guanosine radioligand binding assay reveals that [3H]-Guanosine binding to membrane fractions is greatly enhanced by GPR23 overexpression, and inhibited by GPR23 silencing. Furthermore, in [35S] GTPγS binding assay experiments, Guanosine causes a functional G protein coupled receptor activation in U87GPR23 overexp! ressing cells with an EC50= 8,067 nM. The binding site for [3H]-guanosine is highly specific and both lysophosphatidic acid (LPA) and guanine agonists are 10 times less effective than guanosine in displacing 50 nM [3H]-guanosine binding. In order to correlate the effects of guanosine in the CNS to a putative activation of GPR23, we performed, in different brain areas, the following investigations: by PCR, the expression levels of GPR23; by [3H]-Guanosine radioligand binding assay, the binding properties of Guanosine; by [35S] GTPγS binding assay, the receptor activation properties in response to Guanosine. Among the examined brain areas, the cerebral cortex shows the highest GPR23 expression levels which correlate with the highest Bmax values for [3H]-Guanosine as compared to other brain regions, with the following rank order: cerebral cortex>hippocampus>striatum>spinal cord. [35S] GTPγS binding assay experiments confirm an activation of a G protein-cou! pled receptor in response to guanosine in the cerebral cortex (EC50 10 0 nM). Although these observations do not exclude a possible involvement of other unidentified receptors, they can suggest an involvement of GPR23 in the functional response of cerebral cortex to Guanosine. Overall, together these data suggest that GPR23 may act as a functional membrane receptor for Guanosine.
- Published
- 2013
3. The hormetic role of dietary antioxidants in free radical-related diseases
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Calabrese, Vittorio, Cornelius, Carolin, Trovato Salinaro, A, Cambria, Maria Teresa, Locascio, M, Di Rienzo, L, Condorelli, Df, Mancuso, Cesare, De Lorenzo, A, Calabrese, Ej, Locascio , Ms, Condorelli , Df, Mancuso, Cesare (ORCID:0000-0001-6532-483X), Calabrese, Vittorio, Cornelius, Carolin, Trovato Salinaro, A, Cambria, Maria Teresa, Locascio, M, Di Rienzo, L, Condorelli, Df, Mancuso, Cesare, De Lorenzo, A, Calabrese, Ej, Locascio , Ms, Condorelli , Df, and Mancuso, Cesare (ORCID:0000-0001-6532-483X)
- Published
- 2010
4. Identification of GPR23/LPA4 as a candidate G protein-coupled receptor for Guanosine
- Author
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DI LIBERTO, Valentina, GRILLO, Maria, MUDO', Giuseppa, BELLUARDO, Natale, Garozzo, R, Caciagli, F, Condorelli, DF, Di Liberto, V, Garozzo, R, Grillo, M, Mudò, G, Caciagli, F, Condorelli, DF, and Belluardo, N
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Guanosine, GPCR, LPA - Published
- 2012
5. Brain expression and 3H-Guanosine binding analysis of novel G protein-coupled receptor for guanosine (GPR23/LPA4)
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GRILLO, Maria, DI LIBERTO, Valentina, MUDO', Giuseppa, BELLUARDO, Natale, Garozzo,R, Caciagli,F, Condorelli,DF, Grillo,M, Di Liberto,V, Garozzo,R, Mudò,G, Caciagli,F, Condorelli,DF, and Belluardo,N.
- Subjects
Guanine-based purines receptor ,Brain ,[3H]-Guanosine Binding - Abstract
Several studies have shown that guanine-based purines exert biological effects on the central nervous system, possibly through membrane receptor. In a parallel work, we have identified the first guanosine G protein-coupled receptor GPR23, known as LPA4 receptor, involved in the modulation of guanosine-mediated antiproliferative effects in human glioma cell lines. Here, we performed in different brain areas the following studies: by PCR, the expression levels of GPR23; by [3H]-Guanosine radioligand binding assay, the binding properties of GPR23; by [35S] GTPγS binding assay, the receptor activation properties of guanosine. Among the examined areas, the cerebral cortex showed the highest GPR23 expression levels and affinity binding site for [3H]-Guanosine (KD 143.8 nM and Bmax 3713 nM) as compared to other brain regions with the following rank order: cerebral cortex>hippocampus>striatum>spinal cord. T! he activation of a G protein-coupled receptor in response to guanosine showed in the cerebral cortex an EC50 92 nM. The binding site for [3H]-guanosine was highly specific and both lysophosphatidic acid and guanine agonists were 10 times less effective than guanosine in displacing 50 nM [3H]-guanosine binding. Overall these data demonstrate the existence of different levels of GPR23 mRNAs and of guanosine binding in the brain areas examined. Nevertheless at this stage of study the guanosine binding observed could include, in addition to GPR23, other unidentified receptors.
- Published
- 2012
6. Defective dopaminergic control of contractility in colon from hypoxanthine‐guanine phosphoribosyltransferase deficient (HPRT‐) knockout mice
- Author
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ZIZZO, Maria Grazia, FRINCHI, Monica, DI LIBERTO, Valentina, MUDO', Giuseppa, MULE', Flavia, BELLUARDO, Natale, SERIO, Rosa Maria, CONDORELLI, DF, JINNAH, HA, ZIZZO, MG, FRINCHI, M, DI LIBERTO, V, MUDO’, G, CONDORELLI, DF, JINNAH, HA, MULE’, F, BELLUARDO, N, and SERIO, RM
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Settore BIO/09 - Fisiologia ,HPRT ,DOPAMINE ,COLON - Published
- 2009
7. Distinct pattern of Connexin gene expression during skeletal muscle regeneration in the adult rat
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FRINCHI, Monica, Trovato Salinaro, A, BONOMO, Alessandra, DI LIBERTO, Valentina, BELLUARDO, Natale, Condorelli, DF, MUDO', Giuseppa, Frinchi, M, Trovato-Salinaro, A, Bonomo, A, Di Liberto, V, Belluardo, N, Condorelli, DF, and Mudò,G
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Connexin, muscle regeneration - Abstract
Aim: The aim of present work was to test the hypothesis that Cx37, Cx39, Cx40, Cx43 and Cx45 expression could be regulated in adult regenerating skeletal muscle in response to injury promoting activation of satellite cells involved in myofibers repair and regeneration. Methods: Using in situ hybridization and immunohistochemistry procedures we examined the spatial and temporal expression pattern of above listed connexins in the regenerating gastrocnemious muscle following a mechanical injury. Results: Cx43 and Cx45 mRNA were up-regulated very early, by 3 hour following muscle injury, and were localised in satellite cells, M-cadherin positive cells, distributed around the area of lesion. Three days after lesion a large number of Cx43 and Cx45 mRNA labelled cells were found inside the area of lesion where they become myoblasts, myogenin positive, and participate to muscle regeneration. By contrast, Cx39, not expressed in control muscle, appears in myogenin positive cells 3 days following muscle lesion and its expression was restricted to the area of lesion. Cx39 mRNA was mainly localised in myoblast myogenin positive cells forming clusters or rows of closely apposed cell nuclei committed to form myotubes. Cx40 mRNA labelled cells were observed within 24 hours from injury in the endothelial cells of blood vessels around the area of lesion. After 3 days these cells were localised inside the area of lesion where they co-express myogenin and start to form myotubes. By contrast, Cx37 mRNA expression appeared by 24 hrs from lesion and never was colocalised in myogenin positive cells, but it was involved in new blood vessels formation. All transcripts examined reached a peak of expression between 7-9 days from injury and then progressively declined, being undetectable at 4-5 weeks from injury. Conclusion: Taken together these results support the suggestion that, in regenerating skeletal muscle several connexins may be differentially involved in communication of myogenic committed cells during the process of cell proliferation, aggregation and fusion to form new myotubes.
- Published
- 2008
8. Antiproliferative effects of guanine-based purines and expression of a candidate receptor
- Author
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GAROZZO R, BARRESI V, DI LIBERTO, Valentina, CONDORELLI DF, MUDO', Giuseppa, BELLUARDO, Natale, GAROZZO R, BARRESI V, DI LIBERTO V, MUDO' G, BELLUARDO N, and CONDORELLI DF
- Published
- 2007
9. Association between gene polymorphims of actn3 and srd5a and athletic performance. (2006)
- Author
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MUSSO M, BARRESI V, VECA M, CLEMENTI G, VASTA D, CONDORELLI DF, RUSSO, Giuseppe, POMARA, Francesco, GRAVANTE, Gennaro, MUSSO M, BARRESI V, VECA M, RUSSO G, POMARA F, CLEMENTI G, VASTA D, CONDORELLI DF, and GRAVANTE G
- Published
- 2006
10. Different connexin genes are expressed in early and late phases of the regenerating process in adult skeletal muscles
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MUDO', Giuseppa, BONOMO, Alessandra, BELLUARDO, Natale, TROVATO SALINARO A, CONDORELLI DF, MUDO' G, BONOMO A, TROVATO-SALINARO A, CONDORELLI DF, and BELLUARDO N
- Published
- 2006
11. Different connexin genes are expressed in immuno-identified cell types during skeletal muscle differentiation
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V. BARRESI, TROVATO SALINARO A, MUSSO N, GRASSI F, CONDORELLI DF, MUDO', Giuseppa, BELLUARDO, Natale, V BARRESI, MUDO' G, TROVATO-SALINARO A, MUSSO N, GRASSI F, BELLUARDO N, and CONDORELLI DF
- Published
- 2005
12. Membrane domains in CNS physiology and pathology. Abstracts of the Fourth International Society for Neurochemistry (ISN) Special Conference. Erice (Trapani), Sicily, Italy, 22-26 May 2010
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Trovato Salinaro, A, Musso, N, Mudò, G, Barresi, V, Belluardo, N, and Condorelli, Df
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Central Nervous System ,Membrane Microdomains ,Animals ,Humans ,Neurochemistry - Published
- 2010
13. A NEW ENTITY OF ACUTE T-LINEAGE LYMPHOBLASTIC LEUKEMIA (LLA-T) SENSITIVE TO TYROSINE KINASE INHIBITORS:FULL CHARACTERIZATION OF A PEDIATRIC CASE WITH RESISTANT DISEASE
- Author
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Lo Nigro, L, Barresi, Vincenza, Mirabile, E, Musso, N, Capizzi, C, Corbacioglu, S, Poli, A, Tumino, M, and Condorelli, Df
- Published
- 2010
14. Ridotta espressione e funzione della Connessina 43 nei fibroblasti polmonari fibrotici rispetto ai fibroblasti normali
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Vancheri, C, Trovato Salinaio, E, Trovato Salinaio, A, Mastruzzo, C, Gili, E, Caruso, Massimo, Failla, M, Condorelli, Df, and Crimi, N.
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- 2004
15. New hydrazones, a novel class of experimental antitumor agents RID H-2208-2011
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Hofmann, J, Scheran, G, Easmon, J, Puerstinger, G, Musumarra, Giuseppe, Condorelli, Df, Scire', Salvatore, and Heinisch, G.
- Published
- 2002
16. Euroglia 2002
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Trovato Salinaro, A, Mudò, G, Mirone, MELITA BARBARA, Amato, G, Belluardo, N, and Condorelli, Df.
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Cellular and Molecular Neuroscience ,medicine.anatomical_structure ,Neurology ,biology ,Excitatory amino-acid transporter ,Cell ,medicine ,biology.protein ,Rat retina ,Neuroscience ,Protein kinase C ,Cell biology - Published
- 2002
17. A multivariate insight into the in vitro antitumour screen NCI database
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Musumarra, G., Condorelli, Df, Salvatore Scire, Costa, As, and Fichera, M.
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- 2000
18. Opposite influence of the metabotropic glutamate receptor subtypes mGlu3 and –5 on astrocyte proliferation in culture
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Ciccarelli, R, Sureda, Fx, Casabona, G, DI IORIO, P, Caruso, Alessandra Sebastiana Maria, Spinella, F, Condorelli, Df, Nicoletti, Ferdinando, and Caciagli, F.
- Published
- 1997
19. OPTIMIZED PEG METHOD FOR RAPID PLASMID DNA PURIFICATION - HIGH-YIELD FROM MIDI-PREP
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Nicoletti, Vincenzo Giuseppe and Condorelli, Df
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- 1993
20. DEVELOPMENTAL PROFILE OF METABOTROPIC GLUTAMATE RECEPTOR MESSENGER-RNA IN RAT-BRAIN
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Condorelli, Df, Dellalbani, Amico, P., Casabona, C, Genazzani, G, Sortino, Maria Angela, and Nicoletti, F.
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- 1992
21. Differential regulation of BDNF and NT-3 mRNA levels in primary cultures of rat cerebellar neurons
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Condorelli, DF, Dell'Albani, P, Timmusk, T, Mudo, G, Belluardo, N, Condorelli, DF, Dell'Albani, P, Timmusk, T, Mudo, G, and Belluardo, N
- Published
- 1998
22. Expression of connexin 43 in the human epileptic and drug-resistant cerebral cortex.
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Garbelli R, Frassoni C, Condorelli DF, Trovato Salinaro A, Musso N, Medici V, Tassi L, Bentivoglio M, and Spreafico R
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- 2011
- Full Text
- View/download PDF
23. Expression of metabotropic glutamate receptors in the rat and human testis
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Storto, M, Sallese, M, Salvatore, L, Poulet, R, Condorelli, DF, Dell'Albani, P, Marcello, MF, Romeo, R, Piomboni, P, Barone, N, Nicoletti, F, Nicoletti, F, and De Blasi, A
- Abstract
The G protein-coupled receptor kinase type 4 mediates the homologous desensitisation of type-1 metabotropic glutamate (mGlu1) receptors and is predominantly expressed in the testis. Hence, we searched for the expression of mGlu1 or other mGlu receptor subtypes in rat and human testes. RT-PCR analysis showed the presence of mGlu1, -4 and -5 (but not -2 or -3) receptor mRNA in the rat testis. The presence of mGlu1 and -5 (but not mGlu2/3) receptor proteins was also demonstrated by Western blot analysis. In the rat testis, both mGlu1a and -5 receptors were highly expressed in cells of the germinal line. It is likely that these receptors are functional, because the agonist, (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid, was able to stimulate inositol phospholipid hydrolysis in slices prepared from rat testes. Immunocytochemical analysis of bioptic samples from human testes showed a high expression of mGlu5 receptors inside the seminiferous tubuli, whereas mGlu1a immunoreactivity was restricted to intertubular spaces. mGlu5 receptors were also present in mature spermatozoa, where they were localised in the mid-piece and tail. This localisation coincided with that of beta-arrestin, a protein that is critically involved in the homologous desensitisation and internalisation of G protein-coupled receptors. Taken collectively, these results offer the first evidence for the expression of any glutamate receptor in testes, and suggest that at least mGlu5 receptors are present and functionally active in mature human sperm.
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- 2001
- Full Text
- View/download PDF
24. 'Effects of antidepressants on central GABAergic systems'
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Rampello, Liborio, Fiore, L, Patti, Francesco, Canonico, Pl, Condorelli, Df, Nicoletti, F, Di Giorgio RM, and Giammona, G.
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ANTIDEPRESSANT DRUGS ,GABAERGIC SYSTEM ,CNS - Published
- 1981
25. ADP-RIBOSYLATION OF NUCLEAR AND CYTOSOLIC PROTEINS IN DEVELOPING RAT BRAIN
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Spina Purrello, V, Avola, Roberto, Condorelli, Df, Nicoletti, Vincenzo Giuseppe, Insirello, L, Reale, S, Costa A: Ragusa, N, and Giuffrida Stella AM
- Published
- 1989
26. 'Osservazione di un caso di mioclono-epilessia con atrofia cerebellare'
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Raffaele, R, Rampello, Liborio, Reggio, A, Condorelli, Df, Patti, Francesco, and Pero, G.
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MIOCLONO-EPILESSIA ,ATROFIA CEREBELLARE - Published
- 1981
27. 'Estrogens and Prolactin influence on striatal and nigral GAD activity'
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Di Giorgio RM, Patti, Francesco, Condorelli, Df, Rampello, Liborio, Giammona, G, Macaione, S, Canonico, Pl, and Nicoletti, F.
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Estrogens ,PROLACTIN ,nigral GAD activity - Published
- 1981
28. 'Comparative effects of chronic Haloperidol and Sulpiride treatment on nigral-striatal GABA content'
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Nicoletti, F, Patti, Francesco, Condorelli, Df, Rampello, Liborio, Giammona, G, Di Giorgio RM, Canonico, Pl, and Scapagnini, U.
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Haloperidol ,Sulpiride ,nigral-striatal GABA content - Published
- 1981
29. 'Effects of Dantrolene sodium on central GABAergic system'. Atti delSimposio Internazionale su 'Nuovo approccio terapeutico ai problemi clinici della spasticita''
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Rampello, Liborio, Nicoletti, F, Patti, Francesco, Canonico, Pl, Condorelli, Df, Giammona, G, Reggio, A, Di Giorgio RM, and Raffaele, R.
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central GABAergic system ,Dantrolene sodium - Published
- 1980
30. 'Comparative effects of Haloperidol and Sulpiride on nigro-striatal GABAergic system'
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Nicoletti, F, Patti, Francesco, Giammona, G, Rampello, Liborio, Condorelli, Df, and Di Giorgio RM
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nigro-striatal GABAergic system ,Haloperidol ,Sulpiride - Published
- 1981
31. 'Comparative effect of chronic Haloperidol and Sulpiride treatment on nigral and striatal GABA content'
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Nicoletti, F, Patti, Francesco, Condorelli, Df, Rampello, Liborio, Giammona, G, Canonico, Pl, and Di Giorgio RM
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nigral and striatal GABA content ,sulpiride ,haloperidol - Published
- 1981
32. Distribution and Function of Gap Junction Coupling in Cortical GABAergic Neurons
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Vincenza Barresi, Daniele F. Condorelli, Natale Belluardo, Giuseppa Mudò, Ekrem Dere, Condorelli, DF, Mudò, G, Barresi, V, and Belluardo, N
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genetic structures ,Interneuron ,GAP Junction, GABAergic neurons ,musculoskeletal, neural, and ocular physiology ,Immunoelectron microscopy ,Gap junction ,Hippocampus ,Settore BIO/11 - Biologia Molecolare ,Biology ,Settore BIO/09 - Fisiologia ,medicine.anatomical_structure ,Electrical Synapses ,nervous system ,Cerebral cortex ,Settore BIO/10 - Biochimica ,Synaptic plasticity ,medicine ,GABAergic ,Neuroscience - Abstract
Although gap junctions have been observed in GABAergic interneurons of several brain regions, this chapter focuses on the distribution and functions of gap junctions and connexins in inhibitory interneurons of the cerebral cortex and hippocampus. Evidence for interconnections mediated by electrical synapses is reported for at least eight cerebral cortex interneuron types, classified on the basis of morphology, electrophysiology and molecular markers. The main differences in the organization of these interneuronal networks are summarized in terms of homologous and heterologous electrical coupling and mutual chemical inhibition. The role of connexin36 (Cx36) in forming neuronal electrical synapses in interneurons is reviewed by analyzing data derived by techniques such as immunoelectron microscopy, in situ hybridization, immunohistochemistry, reporter gene expression in transgenic mice, and functional and behavioral studies in knockout mice. Possible functional roles of Cx36-based gap junctions in GABAergic interneuronal networks are examined, from the molecular and cellular level to generation of oscillatory activities and synaptic plasticity.
- Published
- 2013
33. Can guanine-based purines be considered modulators of intestinal motility in rodents?
- Author
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Maria Grazia Zizzo, Rosa Serio, Natale Belluardo, Daniele F. Condorelli, Flavia Mulè, Mariangela Mastropaolo, Zizzo, MG, Mulè, F, Mastropaolo, M, Condorelli, DF, Belluardo, N, and Serio, RM
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Male ,Purine ,(Mouse) ,Time Factors ,Guanine ,Colon ,Guanosine ,In Vitro Techniques ,Pharmacology ,Biology ,Circular muscle ,Settore BIO/09 - Fisiologia ,Adenylyl cyclase ,Mice ,chemistry.chemical_compound ,Animals ,PPADS ,Purine metabolism ,Cholinergic contraction ,Dose-Response Relationship, Drug ,Biological Transport ,Biochemistry ,chemistry ,Cholinergic ,Gastrointestinal Motility ,Nucleoside ,Muscle Contraction - Abstract
Adenine-based purines play a pivotal role in the control of gastrointestinal motility in rodents. Recently, guanine-based purines have been also shown to exert extracellular effects in the central nervous system raising the possibility of the existence of distinct receptors for guanine-based purines. Thus, it seems likely to speculate that also guanine-based purines may play a role in the modulation of the intestinal contractility. Spontaneous and neurally-evoked mechanical activity was recorded in vitro as changes in isometric tension in circular muscle strips from mouse distal colon. Guanosine up to 3 mM or guanine up to 1 mM failed to affect the spontaneous mechanical activity, but reduced the amplitude of the electrical field stimulation (EFS)-induced cholinergic contractions, without affecting the early nitrergic relaxation. Both compounds failed to affect the direct contractile responses evoked by carbachol. No desensitization of the response was observed. Guanine-based purine effects were not altered by theophylline, P1 purinoceptor antagonist, by PPADS or suramin, P2 purinoceptor antagonists, by ODQ, guanilyl cyclase inhibitor, or by DDA, adenylyl cyclase inhibitor. Nucleoside uptake inhibitors, dipyridamole or 6-[(4-Nitrobenzyl)thio]-9-β-D-ribofuranosylpurine (NBTI), antagonized the inhibitory effects induced by guanosine without interfering with guanine. On the contrary, adenine, a competitive inhibitor of nucleobase uptake, antagonized guanine-induced effects. In conclusion, our data indicate that guanosine and guanine are able to modulate negatively the excitatory cholinergic neurotransmission in the circular muscle layer of mouse colon. Guanine-based purines appear to interfere with prejunctional acethylcoline release. Their effects are dependent by their cellular uptake, and independent by adenine-based purine receptors.
- Published
- 2011
34. Identification of calcium sensing receptor (CaSR) mRNA-expressing cells in normal and injured rat brain
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Natale Belluardo, Daniele F. Condorelli, Vincenza Barresi, Giuseppa Mudò, Angela Trovato-Salinaro, Mudò, G, Trovato-Salinaro, A, Barresi, V, Belluardo, N, and Condorelli, DF
- Subjects
Male ,medicine.medical_specialty ,Time Factors ,Central nervous system ,Hippocampus ,Cell Count ,Settore BIO/11 - Biologia Molecolare ,Biology ,Settore BIO/09 - Fisiologia ,chemistry.chemical_compound ,Seizures ,Internal medicine ,Settore BIO/10 - Biochimica ,CaSR ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Ibotenic Acid ,Molecular Biology ,In Situ Hybridization ,Neurons ,Kainic Acid ,General Neuroscience ,Dentate gyrus ,Brain ,Colocalization ,Immunohistochemistry ,Rats ,Oligodendroglia ,medicine.anatomical_structure ,Endocrinology ,nervous system ,chemistry ,Brain Injuries ,Neuroglia ,Neurology (clinical) ,Pyramidal cell ,Calcium sensing receptor (CaSR), isolated for the first time from bovine and human parathyroid, is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expression in neurons and oligodendrocytes, whereas it was not found expressed both in the microglia and in astrocytes. One week after kainate-induced seizure CaSR was found in the injured CA3 region of the hippocampus and very interestingly it was found up-regulated in the neurons of CA1-CA2 and dentate gyrus. Similarly, 1 week following ibotenic acid injection in the hippocampus, CaSR mRNA expression was increased in oligodendrocytes both in the lesioned area and in the contralateral CA1-CA3 pyramidal cell layers and dentate gyrus. One week after needle-induced mechanical lesion an increase of labeled cells expressing CaSR mRNA was observed along the needle track. In conclusion, the present results contribute to extend available data on cell type-expressing CaSR in normal and injured brain and could spur to understand the role of CaSR in repairing processes of brain injury ,Receptors, Calcium-Sensing ,Ibotenic acid ,Developmental Biology ,Astrocyte - Abstract
Calcium sensing receptor (CaSR), isolated for the first time from bovine and human parathyroid, is a G-protein-coupled receptors that has been involved in diverse physiological functions. At present a complete in vivo work on the identification of CaSR mRNA-expressing cells in the adult brain lacks and this investigation was undertaken in order to acquire more information on cell type expressing CaSR mRNA in the rat brain and to analyse for the first time its expression in different experimental models of brain injury. The expression of CaSR mRNAs was found mainly in scattered cells throughout almost all the brain regions. A double labeling analysis showed a colocalization of CaSR mRNA expression in neurons and oligodendrocytes, whereas it was not found expressed both in the microglia and in astrocytes. One week after kainate-induced seizure CaSR was found in the injured CA3 region of the hippocampus and very interestingly it was found up-regulated in the neurons of CA1-CA2 and dentate gyrus. Similarly, 1 week following ibotenic acid injection in the hippocampus, CaSR mRNA expression was increased in oligodendrocytes both in the lesioned area and in the contralateral CA1-CA3 pyramidal cell layers and dentate gyrus. One week after needle-induced mechanical lesion an increase of labeled cells expressing CaSR mRNA was observed along the needle track. In conclusion, the present results contribute to extend available data on cell type-expressing CaSR in normal and injured brain and could spur to understand the role of CaSR in repairing processes of brain injury.
- Published
- 2009
35. Regulation of connexin gene expression during skeletal muscle regeneration in the adult rat
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Klaus Willecke, A. Trovato-Salinaro, Giuseppa Mudò, Daniele F. Condorelli, Monica Frinchi, Natale Belluardo, J. von Maltzahn, Trovato-Salinaro, A, Belluardo, N, Frinchi, M, Von Maltzahn, J, Willecke, K, Condorelli, DF, and Mudo', G
- Subjects
Male ,Pathology ,medicine.medical_specialty ,Time Factors ,Physiology ,Muscle Fibers, Skeletal ,Connexin ,Neovascularization, Physiologic ,connexin 45 ,Biology ,Connexins ,connexin 43 ,Cell Fusion ,connexin 40 ,Muscle regeneration ,Gene expression ,medicine ,Connexin 30 ,Myocyte ,Animals ,Regeneration ,RNA, Messenger ,Rats, Wistar ,Muscle, Skeletal ,In Situ Hybridization ,Cell Aggregation ,Cell Proliferation ,Myogenic cells ,connexin 39 ,Regeneration (biology) ,Skeletal muscle ,Endothelial Cells ,Cell Biology ,connexin 37 ,biology.organism_classification ,Constriction ,Immunohistochemistry ,Cell biology ,Rats ,medicine.anatomical_structure ,Gene Expression Regulation ,myogenic cell ,Satellite (biology) - Abstract
In the adult skeletal muscle, various kinds of trauma promote proliferation of satellite cells that differentiate into myoblasts forming new myofibers or to repair the damaged one. The aim of present work was to perform a comparative spatial and temporal analysis of connexin (Cx) 37, Cx39, Cx40, Cx43, and Cx45 expression in the adult regenerating skeletal muscle in response to crush injury. Within 24 h from injury, Cx37 expression was upregulated in the endothelial cells of blood vessels, and, 5 days after injury, Cx37-expressing cells were found inside the area of lesion and formed clusters generating new blood vessels with endothelial cells expressing Cx37. Three days after injury, Cx39 mRNA was selectively expressed in myogenin-positive cells, forming rows of closely apposed cell nuclei fusing in myotubes. Cx40 mRNA-labeled cells were observed within 24 h from injury in the endothelium of blood vessels, and, 5 days after lesion, Cx40-labeled cells were found inside the area of lesion-forming rows of myogenin-positive, closely apposed cells coexpressing Cx39. Within 24 h from lesion, both Cx43 and Cx45 mRNAs were upregulated in individual cells, and some of them were positive for M-cadherin. Three days after injury, a large number of both Cx43 and Cx45 mRNA-labeled and myogenin-positive cells were found inside the area of lesion. Taken together, these results show that at least four Cxs, out of five expressed in regenerating skeletal muscle, can be differentially involved in communication of myogenic cells during the process of cell proliferation, aggregation, and fusion to form new myotubes or to repair damaged myofibers.
- Published
- 2009
36. Cellular localization of mGluR3 and mGluR5 mRNAs in normal and injured rat brain
- Author
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Qingzhang Cheng, Giuseppa Mudò, Daniele F. Condorelli, Giuseppa Caniglia, Angela Trovato-Salinaro, MUDO' G, TROVATO-SALINARO A, CANIGLIA G, CHENG Q, and CONDORELLI DF
- Subjects
Male ,Cell type ,Receptor, Metabotropic Glutamate 5 ,In situ hybridization ,Hippocampal formation ,Biology ,Receptors, Metabotropic Glutamate ,Settore BIO/09 - Fisiologia ,mental disorders ,medicine ,Animals ,RNA, Messenger ,Rats, Wistar ,Molecular Biology ,Cellular localization ,In Situ Hybridization ,Neurons ,General Neuroscience ,Glutamate receptor ,Brain ,Immunohistochemistry ,Oligodendrocyte ,Cell biology ,Rats ,medicine.anatomical_structure ,nervous system ,Brain Injuries ,Neuroglia ,Neurology (clinical) ,Neuroscience ,Developmental Biology ,Astrocyte - Abstract
In order to understand the role of metabotropic glutamate receptors (mGluRs) in the brain, it is important to know how the mGluRs are differentially expressed among the different cell types. At present, the cellular expression of mGluR3 and mGluR5 has been mostly studied in terms of proteins with observations suggesting the expression of both mGluR3 and mGluR5 in neuronal and in glial cells. In order to verify the brain cell type-expressing mGluR3 and mGluR5 mRNAs, both in normal and injured brain, we performed a double labeling analysis, by in situ hybridization for mGluR3 or mGluR5 mRNA and immunohistochemistry for specific cellular markers. This approach allowed us to find mGluR3 mRNA expressed in neurons (NeuN-positive cells), and in glial cells, such as astrocytes (GFAP-positive cells) and oligodendrocytes (CNPase-positive cells). The same analysis showed that only NeuN-positive cells express mGluR5 mRNA. The time course of mGluR3 mRNA expression in two models of hippocampal formation lesion, kainate-induced seizures or ibotenic acid injection, showed an increased expression of mGluR3 in the area of lesion. This effect appears 1 week after the injury and was localized in GFAP- and CNPase-positive cells. In contrast, mGluR5 was not found expressed in the area of lesion. The present results contribute to extend available data on cell type-expressing mGluR3 and mGluR5 in normal and injured brain and could be relevant to understand the mechanisms that drive neuron–glial cells interaction both in normal and repairing processes.
- Published
- 2007
37. Gain-Type Aneuploidies Influence the Burden of Selective Long Non-Coding Transcripts in Colorectal Cancer.
- Author
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Scuderi C, Di Bella V, Privitera AP, Giustolisi FM, Barresi V, and Condorelli DF
- Subjects
- Humans, DNA Copy Number Variations, Transcriptome, Female, Cell Line, Tumor, Gene Expression Profiling, Male, Chromosomal Instability, Middle Aged, Chromosome Aberrations, Polymorphism, Single Nucleotide, RNA, Long Noncoding genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Aneuploidy, Gene Expression Regulation, Neoplastic
- Abstract
Chromosomal instability is a hallmark of colorectal carcinogenesis and produces an accumulation of different forms of aneuploidies or broad copy number aberrations. Colorectal cancer is characterized by gain-type broad copy number aberrations, specifically in Chr20, Chr8q, Chr13 and Chr7, but their roles and mechanisms in cancer progression are not fully understood. It has been suggested that broad copy number gains might contribute to tumor development through the so-called caricature transcriptomic effect. We intend to investigate the impact of broad copy number gains on long non-coding RNAs' expression in colorectal cancer, given their well-known role in oncogenesis. The influence of such chromosomal aberrations on lncRNAs' transcriptome profile was investigated by SNP and transcriptome arrays in our series of colorectal cancer samples and cell lines. The correlation between aneuploidies and transcriptomic profiles led us to obtain a class of Over-UpT lncRNAs, which are transcripts upregulated in CRC and further overexpressed in colon tumors bearing specific chromosomal aberrations. The identified lncRNAs can contribute to a wide interaction network to establish the cancer driving effect of gain-type aneuploidies.
- Published
- 2024
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38. Measuring cancer driving force of chromosomal aberrations through multi-layer Boolean implication networks.
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Cosentini I, Condorelli DF, Locicero G, Ferro A, Pulvirenti A, Barresi V, and Alaimo S
- Subjects
- Humans, DNA Methylation, Transcriptome, Epigenome, Chromosome Aberrations, Neoplasms genetics, Neoplasms metabolism
- Abstract
Multi-layer Complex networks are commonly used for modeling and analysing biological entities. This paper presents the advantage of using COMBO (Combining Multi Bio Omics) to suggest a new role of the chromosomal aberration as a cancer driver factor. Exploiting the heterogeneous multi-layer networks, COMBO integrates gene expression and DNA-methylation data in order to identify complex bilateral relationships between transcriptome and epigenome. We evaluated the multi-layer networks generated by COMBO on different TCGA cancer datasets (COAD, BLCA, BRCA, CESC, STAD) focusing on the effect of a specific chromosomal numerical aberration, broad gain in chromosome 20, on different cancer histotypes. In addition, the effect of chromosome 8q amplification was tested in the same TCGA cancer dataset. The results demonstrate the ability of COMBO to identify the chromosome 20 amplification cancer driver force in the different TCGA Pan Cancer project datasets., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Cosentini et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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39. Retraction Note: Modulation of the TGF-β1-induced epithelial to mesenchymal transition (EMT) mediated by P1 and P2 purine receptors in MDCK cells.
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Zuccarini M, Giuliani P, Buccella S, Di Liberto V, Mudò G, Belluardo N, Carluccio M, Rossini M, Condorelli DF, Rathbone MP, Caciagli F, Ciccarelli R, and Di Iorio P
- Published
- 2023
- Full Text
- View/download PDF
40. Temporary serine protease inhibition and the role of SPINK2 in human bone marrow.
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Barresi V, Di Bella V, Lo Nigro L, Privitera AP, Bonaccorso P, Scuderi C, and Condorelli DF
- Abstract
Protease temporary inhibitors are true substrates that bind the catalytic site with high affinity but are slowly degraded, thus acting as inhibitor for a defined time window. Serine peptidase inhibitor Kazal type (SPINK) family is endowed with such functional property whose physiological meaning is poorly explored. High expression of SPINK2 in some hematopoietic malignancies prompted us to investigate its role in adult human bone marrow. We report here the physiological expression of SPINK2 in hematopoietic stem and progenitor cells (HSPCs) and mobilized cluster differentiation 34 (CD34)
+ cells. We determined the SPINK2 degradation constant and derived a mathematical relationship predicting the zone of inhibited target protease activity surrounding the SPINK2-secreting HSPCs. Analysis of putative target proteases for SPINK2 revealed the expression of PRSS2 and PRSS57 in HSPCs. Our combined results suggest that SPINK2 and its target serine proteases might play a role in the intercellular communication within the hematopoietic stem cell niche., Competing Interests: The authors declare no competing interests., (© 2023 The Authors.)- Published
- 2023
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41. Downregulation of the Astroglial Connexin Expression and Neurodegeneration after Pilocarpine-Induced Status Epilepticus.
- Author
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Andrioli A, Fabene PF, Mudò G, Barresi V, Di Liberto V, Frinchi M, Bentivoglio M, and Condorelli DF
- Subjects
- Animals, Rats, Astrocytes metabolism, Connexin 43 metabolism, Down-Regulation, Hippocampus metabolism, Pilocarpine toxicity, RNA, Messenger metabolism, Seizures metabolism, Connexins metabolism, Status Epilepticus chemically induced, Status Epilepticus genetics, Status Epilepticus metabolism
- Abstract
Astrocytic networks and gap junctional communication mediated by connexins (Cxs) have been repeatedly implicated in seizures, epileptogenesis, and epilepsy. However, the effect of seizures on Cx expression is controversial. The present study focused on the response of Cxs to status epilepticus (SE), which is in turn an epileptogenic insult. The expression of neuronal Cx36 and astrocytic Cx30 and Cx43 mRNAs was investigated in the brain of rats in the first day after pilocarpine-induced SE. In situ hybridization revealed a progressive decrease in Cx43 and Cx30 mRNA levels, significantly marked 24 h after SE onset in neocortical areas and the hippocampus, and in most thalamic domains, whereas Cx36 mRNA did not exhibit obvious changes. Regional evaluation with quantitative real-time-RT-PCR confirmed Cx43 and Cx30 mRNA downregulation 24 h after SE, when ongoing neuronal cell death was found in the same brain regions. Immunolabeling showed at the same time point marked a decrease in Cx43, microglia activation, and interleukin-1β induction in some microglial cells. The data showed a transient downregulation of astroglial Cxs in the cortical and thalamic areas in which SE triggers neurodegenerative events in concomitance with microglia activation and cytokine expression. This could potentially represent a protective response of neuroglial networks to SE-induced acute damage.
- Published
- 2022
- Full Text
- View/download PDF
42. Guanine inhibits the growth of human glioma and melanoma cell lines by interacting with GPR23.
- Author
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Garozzo R, Zuccarini M, Giuliani P, Di Liberto V, Mudò G, Caciagli F, Ciccarelli R, Ciruela F, Di Iorio P, and Condorelli DF
- Abstract
Guanine-based purines (GBPs) exert numerous biological effects at the central nervous system through putative membrane receptors, the existence of which is still elusive. To shed light on this question, we screened orphan and poorly characterized G protein-coupled receptors (GPRs), selecting those that showed a high purinoreceptor similarity and were expressed in glioma cells, where GBPs exerted a powerful antiproliferative effect. Of the GPRs chosen, only the silencing of GPR23, also known as lysophosphatidic acid (LPA) 4 receptor, counteracted GBP-induced growth inhibition in U87 cells. Guanine (GUA) was the most potent compound behind the GPR23-mediated effect, acting as the endpoint effector of GBP antiproliferative effects. Accordingly, cells stably expressing GPR23 showed increased sensitivity to GUA. Furthermore, while GPR23 expression was low in a hypoxanthine-guanine phosphoribosyl-transferase (HGPRT)-mutated melanoma cell line showing poor sensitivity to GBPs, and in HGPRT-silenced glioma cells, GPR23-induced expression in both cell types rescued GUA-mediated cell growth inhibition. Finally, binding experiments using [
3 H]-GUA and U87 cell membranes revealed the existence of a selective GUA binding (KD = 29.44 ± 4.07 nM; Bmax 1.007 ± 0.035 pmol/mg prot) likely to GPR23. Overall, these data suggest GPR23 involvement in modulating responses to GUA in tumor cell lines, although further research needs to verify whether this receptor mediates other GUA effects., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Garozzo, Zuccarini, Giuliani, Di Liberto, Mudò, Caciagli, Ciccarelli, Ciruela, Di Iorio and Condorelli.)- Published
- 2022
- Full Text
- View/download PDF
43. Transcript-Targeted Therapy Based on RNA Interference and Antisense Oligonucleotides: Current Applications and Novel Molecular Targets.
- Author
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Barresi V, Musmeci C, Rinaldi A, and Condorelli DF
- Subjects
- Child, Female, Genetic Therapy, Humans, Oligonucleotides, Antisense genetics, Oligonucleotides, Antisense therapeutic use, Proprotein Convertase 9 genetics, Quality of Life, RNA, RNA Interference, RNA Splicing, RNA, Messenger genetics, Muscular Dystrophy, Duchenne genetics, Neurodegenerative Diseases drug therapy
- Abstract
The development of novel target therapies based on the use of RNA interference (RNAi) and antisense oligonucleotides (ASOs) is growing in an exponential way, challenging the chance for the treatment of the genetic diseases and cancer by hitting selectively targeted RNA in a sequence-dependent manner. Multiple opportunities are taking shape, able to remove defective protein by silencing RNA (e.g., Inclisiran targets mRNA of protein PCSK9, permitting a longer half-life of LDL receptors in heterozygous familial hypercholesteremia), by arresting mRNA translation (i.e., Fomivirsen that binds to UL123-RNA and blocks the translation into IE2 protein in CMV-retinitis), or by reactivating modified functional protein (e.g., Eteplirsen able to restore a functional shorter dystrophin by skipping the exon 51 in Duchenne muscular dystrophy) or a not very functional protein. In this last case, the use of ASOs permits modifying the expression of specific proteins by modulating splicing of specific pre-RNAs (e.g., Nusinersen acts on the splicing of exon 7 in SMN2 mRNA normally not expressed; it is used for spinal muscular atrophy) or by downregulation of transcript levels (e.g., Inotersen acts on the transthryretin mRNA to reduce its expression; it is prescribed for the treatment of hereditary transthyretin amyloidosis) in order to restore the biochemical/physiological condition and ameliorate quality of life. In the era of precision medicine, recently, an experimental splice-modulating antisense oligonucleotide, Milasen, was designed and used to treat an 8-year-old girl affected by a rare, fatal, progressive form of neurodegenerative disease leading to death during adolescence. In this review, we summarize the main transcriptional therapeutic drugs approved to date for the treatment of genetic diseases by principal regulatory government agencies and recent clinical trials aimed at the treatment of cancer. Their mechanism of action, chemical structure, administration, and biomedical performance are predominantly discussed.
- Published
- 2022
- Full Text
- View/download PDF
44. NUP-98 Rearrangements Led to the Identification of Candidate Biomarkers for Primary Induction Failure in Pediatric Acute Myeloid Leukemia.
- Author
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Barresi V, Di Bella V, Andriano N, Privitera AP, Bonaccorso P, La Rosa M, Iachelli V, Spampinato G, Pulvirenti G, Scuderi C, Condorelli DF, and Lo Nigro L
- Subjects
- Adolescent, Child, Child, Preschool, Cohort Studies, Cyclin-Dependent Kinase 6 genetics, Female, Gene Expression Regulation, Leukemic drug effects, Gene Rearrangement, Histone-Lysine N-Methyltransferase genetics, Humans, Infant, Infant, Newborn, Male, Multigene Family, Real-Time Polymerase Chain Reaction, Reproducibility of Results, Treatment Failure, Biomarkers, Tumor genetics, Leukemia, Myeloid, Acute drug therapy, Leukemia, Myeloid, Acute genetics, Nuclear Pore Complex Proteins genetics
- Abstract
Conventional chemotherapy for acute myeloid leukemia regimens generally encompass an intensive induction phase, in order to achieve a morphological remission in terms of bone marrow blasts (<5%). The majority of cases are classified as Primary Induction Response (PIR); unfortunately, 15% of children do not achieve remission and are defined Primary Induction Failure (PIF). This study aims to characterize the gene expression profile of PIF in children with Acute Myeloid Leukemia (AML), in order to detect molecular pathways dysfunctions and identify potential biomarkers. Given that NUP98-rearrangements are enriched in PIF-AML patients, we investigated the association of NUP98-driven genes in primary chemoresistance. Therefore, 85 expression arrays, deposited on GEO database, and 358 RNAseq AML samples, from TARGET program, were analyzed for "Differentially Expressed Genes" (DEGs) between NUP98+ and NUP98-, identifying 110 highly confident NUP98/PIF-associated DEGs. We confirmed, by qRT-PCR, the overexpression of nine DEGs, selected on the bases of the diagnostic accuracy, in a local cohort of PIF patients: SPINK2 , TMA7 , SPCS2 , CDCP1 , CAPZA1 , FGFR1OP2 , MAN1A2 , NT5C3A and SRP54 . In conclusion, the integrated analysis of NUP98 mutational analysis and transcriptome profiles allowed the identification of novel putative biomarkers for the prediction of PIF in AML.
- Published
- 2021
- Full Text
- View/download PDF
45. Investigating the Role of Guanosine on Human Neuroblastoma Cell Differentiation and the Underlying Molecular Mechanisms.
- Author
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Belluardo N, Mudò G, Di Liberto V, Frinchi M, Condorelli DF, Traversa U, Ciruela F, Ciccarelli R, Di Iorio P, and Giuliani P
- Abstract
Neuroblastoma arises from neural crest cell precursors failing to complete the process of differentiation. Thus, agents helping tumor cells to differentiate into normal cells can represent a valid therapeutic strategy. Here, we evaluated whether guanosine (GUO), a natural purine nucleoside, which is able to induce differentiation of many cell types, may cause the differentiation of human neuroblastoma SH-SY5Y cells and the molecular mechanisms involved. We found that GUO, added to the cell culture medium, promoted neuron-like cell differentiation in a time- and concentration-dependent manner. This effect was mainly due to an extracellular GUO action since nucleoside transporter inhibitors reduced but not abolished it. Importantly, GUO-mediated neuron-like cell differentiation was independent of adenosine receptor activation as it was not altered by the blockade of these receptors. Noteworthy, the neuritogenic activity of GUO was not affected by blocking the phosphoinositide 3-kinase pathway, while it was reduced by inhibitors of protein kinase C or soluble guanylate cyclase. Furthermore, the inhibitor of the enzyme heme oxygenase-1 but not that of nitric oxide synthase reduced GUO-induced neurite outgrowth. Interestingly, we found that GUO was largely metabolized into guanine by the purine nucleoside phosphorylase (PNP) enzyme released from cells. Taken together, our results suggest that GUO, promoting neuroblastoma cell differentiation, may represent a potential therapeutic agent; however, due to its spontaneous extracellular metabolism, the role played by the GUO-PNP-guanine system needs to be further investigated., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Belluardo, Mudò, Di Liberto, Frinchi, Condorelli, Traversa, Ciruela, Ciccarelli, Di Iorio and Giuliani.)
- Published
- 2021
- Full Text
- View/download PDF
46. Aberrations of Chromosomes 1 and 16 in Breast Cancer: A Framework for Cooperation of Transcriptionally Dysregulated Genes.
- Author
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Privitera AP, Barresi V, and Condorelli DF
- Abstract
Derivative chromosome der(1;16), isochromosome 1q, and deleted 16q-producing arm-level 1q-gain and/or 16q-loss-are recurrent cytogenetic abnormalities in breast cancer, but their exact role in determining the malignant phenotype is still largely unknown. We exploited The Cancer Genome Atlas (TCGA) data to generate and analyze groups of breast invasive carcinomas, called 1,16-chromogroups, that are characterized by a pattern of arm-level somatic copy number aberrations congruent with known cytogenetic aberrations of chromosome 1 and 16. Substantial differences were found among 1,16-chromogroups in terms of other chromosomal aberrations, aneuploidy scores, transcriptomic data, single-point mutations, histotypes, and molecular subtypes. Breast cancers with a co-occurrence of 1q-gain and 16q-loss can be distinguished in a "low aneuploidy score" group, congruent to der(1;16), and a "high aneuploidy score" group, congruent to the co-occurrence of isochromosome 1q and deleted 16q. Another three groups are formed by cancers showing separately 1q-gain or 16q-loss or no aberrations of 1q and 16q. Transcriptome comparisons among the 1,16-chromogroups, integrated with functional pathway analysis, suggested the cooperation of overexpressed 1q genes and underexpressed 16q genes in the genesis of both ductal and lobular carcinomas, thus highlighting the putative role of genes encoding gamma-secretase subunits (APH1A, PSEN2, and NCSTN) and Wnt enhanceosome components (BCL9 and PYGO2) in 1q, and the glycoprotein E-cadherin (CDH1), the E3 ubiquitin-protein ligase WWP2, the deubiquitinating enzyme CYLD, and the transcription factor CBFB in 16q. The analysis of 1,16-chromogroups is a strategy with far-reaching implications for the selection of cancer cell models and novel experimental therapies.
- Published
- 2021
- Full Text
- View/download PDF
47. Gastric ghrelin cells in obese patients are hyperactive.
- Author
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Castorina S, Barresi V, Luca T, Privitera G, De Geronimo V, Lezoche G, Cosentini I, Di Vincenzo A, Barbatelli G, Giordano A, Taus M, Nicolai A, Condorelli DF, and Cinti S
- Subjects
- Adult, Case-Control Studies, Cells, Cultured, Diabetes Mellitus, Type 2, Female, Gastrectomy, Humans, Male, Middle Aged, Weight Loss, Ghrelin analysis, Ghrelin genetics, Ghrelin metabolism, Obesity metabolism, Obesity physiopathology, Obesity surgery, Stomach cytology, Stomach metabolism, Stomach pathology
- Abstract
Background/objectives: Distribution and activity of ghrelin cells in the stomach of obese subjects are controversial., Subjects/methods: We examined samples from stomachs removed by sleeve gastrectomy in 49 obese subjects (normoglycemic, hyperglycemic and diabetic) and quantified the density of ghrelin/chromogranin endocrine cells by immunohistochemistry. Data were compared with those from 13 lean subjects evaluated by gastroscopy. In 44 cases (11 controls and 33 obese patients) a gene expression analysis of ghrelin and its activating enzyme ghrelin O-acyl transferase (GOAT) was performed. In 21 cases (4 controls and 17 obese patients) the protein levels of unacylated and acylated-ghrelin were measured by ELISA tests. In 18 cases (4 controls and 14 obese patients) the morphology of ghrelin-producing cells was evaluated by electron microscopy., Results: The obese group, either considered as total population or divided into subgroups, did not show any significant difference in ghrelin cell density when compared with control subjects. Inter-glandular smooth muscle fibres were increased in obese patients. In line with a positive trend of the desacylated form found by ELISA, Ghrelin and GOAT mRNA expression in obese patients was significantly increased. The unique ghrelin cell ultrastructure was maintained in all obese groups. In the hyperglycemic obese patients, the higher ghrelin expression matched with ultrastructural signs of endocrine hyperactivity, including expanded rough endoplasmic reticulum and reduced density, size and electron-density of endocrine granules. A positive correlation between ghrelin gene expression and glycemic values, body mass index and GOAT was also found. All obese patients with type 2 diabetes recovered from diabetes at follow-up after 5 months with a 16.5% of weight loss., Conclusions: Given the known inhibitory role on insulin secretion of ghrelin, these results suggest a possible role for gastric ghrelin overproduction in the complex architecture that takes part in the pathogenesis of type 2 diabetes.
- Published
- 2021
- Full Text
- View/download PDF
48. Guanosine-Mediated Anxiolytic-Like Effect: Interplay with Adenosine A 1 and A 2A Receptors.
- Author
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Frinchi M, Verdi V, Plescia F, Ciruela F, Grillo M, Garozzo R, Condorelli DF, Di Iorio P, Caciagli F, Ciccarelli R, Belluardo N, Di Liberto V, and Mudò G
- Subjects
- Animals, Anxiety psychology, Behavior, Animal, Cell Membrane metabolism, Darkness, Dose-Response Relationship, Drug, Guanosine metabolism, Hippocampus metabolism, Light, Rats, Receptor, Adenosine A1 genetics, Receptor, Adenosine A2A genetics, Anxiety etiology, Anxiety metabolism, Guanosine adverse effects, Receptor, Adenosine A1 metabolism, Receptor, Adenosine A2A metabolism
- Abstract
Acute or chronic administration of guanosine (GUO) induces anxiolytic-like effects, for which the adenosine (ADO) system involvement has been postulated yet without a direct experimental evidence. Thus, we aimed to investigate whether adenosine receptors (ARs) are involved in the GUO-mediated anxiolytic-like effect, evaluated by three anxiety-related paradigms in rats. First, we confirmed that acute treatment with GUO exerts an anxiolytic-like effect. Subsequently, we investigated the effects of pretreatment with ADO or A
1 R (CPA, CCPA) or A2A R (CGS21680) agonists 10 min prior to GUO on a GUO-induced anxiolytic-like effect. All the combined treatments blocked the GUO anxiolytic-like effect, whereas when administered alone, each compound was ineffective as compared to the control group. Interestingly, the pretreatment with nonselective antagonist caffeine or selective A1 R (DPCPX) or A2A R (ZM241385) antagonists did not modify the GUO-induced anxiolytic-like effect. Finally, binding assay performed in hippocampal membranes showed that [3 H]GUO binding became saturable at 100-300 nM, suggesting the existence of a putative GUO binding site. In competition experiments, ADO showed a potency order similar to GUO in displacing [3 H]GUO binding, whereas AR selective agonists, CPA and CGS21680, partially displaced [3 H]GUO binding, but the sum of the two effects was able to displace [3 H]GUO binding to the same extent of ADO alone. Overall, our results strengthen previous data supporting GUO-mediated anxiolytic-like effects, add new evidence that these effects are blocked by A1 R and A2A R agonists and pave, although they do not elucidate the mechanism of GUO and ADO receptor interaction, for a better characterization of GUO binding sites in ARs.- Published
- 2020
- Full Text
- View/download PDF
49. Dectin-1 and TIM3 Expression in Deep Vein Thrombosis of Lower Limbs (DVTLL).
- Author
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Barresi V, Napoli S, Spampinato G, Condorelli DF, and Signorelli SS
- Abstract
The pathophysiological mechanisms of venous thromboembolism are venous stasis, endothelial damage, and hypercoagulability, while less attention has been given to the role of both innate and native immunity. In this paper, we investigate the involvement of the activated immune system detected through some indicators such as TIM3 and Dectin-1 expressed by T lymphocytes. TIM3 and Dectin-1, two surface molecules that regulate the fine-tuning of innate and adaptive immune responses, were evaluated in patients affected by deep vein thrombosis of lower limbs (DVTLL). CD3
+ , CD4+ and CD8+ T lymphocytes obtained from patients affected by DVTLL were analysed using fluorescence-conjugated antibodies for TIM3 and Dectin-1 by an imaging flow cytometer. DVTLL patients showed a higher number of CD4+ and CD8+ T lymphocytes. TIM3 expression in T lymphocytes was very low in both DVTLL patients and controls. On the contrary, an increase in Dectin-1+ cells among CD4+ and CD8+ T lymphocytes from DVTLL patients was observed. Dectin-1 is known to play a role in inflammation and immunity and our result suggests its potential involvement in thrombotic venous disease.- Published
- 2020
- Full Text
- View/download PDF
50. Synthesis of Bisphenol Neolignans Inspired by Honokiol as Antiproliferative Agents.
- Author
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Cardullo N, Barresi V, Muccilli V, Spampinato G, D'Amico M, Condorelli DF, and Tringali C
- Subjects
- Antineoplastic Agents chemistry, Antineoplastic Agents pharmacology, Apoptosis drug effects, Cell Line, Tumor, Drug Screening Assays, Antitumor methods, HCT116 Cells, HT29 Cells, Humans, Lignans chemistry, PC-3 Cells, Benzhydryl Compounds chemical synthesis, Benzhydryl Compounds pharmacology, Biphenyl Compounds chemistry, Cell Proliferation drug effects, Lignans chemical synthesis, Lignans pharmacology, Phenols chemical synthesis, Phenols pharmacology
- Abstract
Honokiol (2) is a natural bisphenol neolignan showing a variety of biological properties, including antitumor activity. Some studies pointed out 2 as a potential anticancer agent in view of its antiproliferative and pro-apoptotic activity towards tumor cells. As a further contribution to these studies, we report here the synthesis of a small library of bisphenol neolignans inspired by honokiol and the evaluation of their antiproliferative activity. The natural lead was hence subjected to simple chemical modifications to obtain the derivatives 3-9; further neolignans (12a-c, 13a-c, 14a-c, and 15a) were synthesized employing the Suzuki-Miyaura reaction, thus obtaining bisphenols with a substitution pattern different from honokiol. These compounds and the natural lead were subjected to antiproliferative assay towards HCT-116, HT-29, and PC3 tumor cell lines. Six of the neolignans show GI
50 values lower than those of 2 towards all cell lines. Compounds 14a, 14c, and 15a are the most effective antiproliferative agents, with GI50 in the range of 3.6-19.1 µM, in some cases it is lower than those of the anticancer drug 5-fluorouracil. Flow cytometry experiments performed on these neolignans showed that the inhibition of proliferation is mainly due to an apoptotic process. These results indicate that the structural modification of honokiol may open the way to obtaining antitumor neolignans more potent than the natural lead.- Published
- 2020
- Full Text
- View/download PDF
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