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592 results on '"G, Tettamanti"'

1. The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi

Author

Yannick Weyer, Sinead I. Schwabl, Xuechen Tang, Astha Purwar, Konstantin Siegmann, Angela Ruepp, Theresia Dunzendorfer-Matt, Michael A. Widerin, Veronika Niedrist, Noa J. M. Mutsters, Maria G. Tettamanti, Sabine Weys, Bettina Sarg, Leopold Kremser, Klaus R. Liedl, Oliver Schmidt, and David Teis

Subjects
Science
Abstract

Abstract The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex uses its rhomboid pseudo-protease subunit, Dsc2, to assess the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex likely interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be extracted by Cdc48 for endosome and Golgi associated proteasomal degradation (EGAD), while others will undergo ESCRT dependent vacuolar degradation. Some substrates are degraded by both, EGAD- or ESCRT pathways. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thereby preserves cellular membrane protein and lipid composition.

Published
2024
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2. Autophagy in development and regeneration: role in tissue remodelling and cell survival

Author

G. Tettamanti, E. Carata, A. Montali, L. Dini, and G. M. Fimia

Subjects
Autophagy, development, invertebrates, vertebrates, regeneration, Zoology, QL1-991
Abstract

Morphogenetic events that occur during development and regeneration are energy demanding processes requiring profound rearrangements in cell architecture, which need to be coordinated in timely fashion with other cellular activities, such as proliferation, migration and differentiation. In the last 15 years, it has become evident that autophagy, an evolutionarily-conserved catabolic process that mediates the lysosomal turnover of organelles and macromolecules, is an essential “tool” to ensure remodelling events that occur at cellular and tissue levels. Indeed, studies in several model organisms have shown that the inactivation of autophagy genes has a significant impact on embryogenesis and tissue regeneration, leading to extensive cell death and persistence of unnecessary cell components. Interestingly, the increased understanding of the mechanisms that confers selectivity to the autophagic process has also contributed to identifying development-specific targets of autophagy across species. Moreover, alternative ways to deliver materials to the lysosome, such as microautophagy, are also emerging as key actors in these contexts, providing a more complete view of how the cell component repertoire is renovated. In this review, we discuss the role of different types of autophagy in development and regeneration of invertebrates and vertebrates, focusing in particular on its contribution in cnidarians, platyhelminthes, nematodes, insects, zebrafish and mammals.

Published
2019
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4. Proteomic analysis of the silkworm midgut during larval-pupal transition

Author

M Kannan, V Suryaaathmanathan, M Saravanakumar, D Romanelli, G Tettamanti, and M Krishnan

Subjects
Bombyx mori, immune response, midgut remodeling, two-dimensional polyacrylamide gel electrophoresis, zymogram, matrix assisted laser desorption/ionization-mass spectrometry, Biology (General), QH301-705.5
Abstract

Metamorphosis is a key process in holometabolous insects since specific larval tissues, such as the midgut, the silk gland and the fat body, are remodeled into adult organs, or even disintegrate. However, the role of proteins and factors involved in the remodeling of these organs is still unclear. For this reason we undertook a proteomic study on the larval midgut of Bombyx mori to identify proteins whose expression significantly changes during larval-pupal metamorphosis and thus can have a role in this process. 2D-PAGE analysis showed upregulation or new expression of midgut proteins at 45 (pI 5.2), 29.8 (pI 6.11) and 20-kDa (pI 6-7) during the pupal stage. In addition zymogram analysis demonstrated the occurrence of protease activity at 37-kDa at the same developmental stage. By using MALDI-TOF-MS analysis the protein spots from 2D gel were identified as Hemolin, low molecular weight 30-kDa lipoproteins, HSP 20.8 and HSP 20.4, while the proteolytic band was identified as 37-kDa serine protease. The evidence herein presented suggests that the identified proteins could be involved in the immune protection during the remodeling of silkworm midgut that occurs at larval-pupal transition and represents a platform of knowledge necessary for future functional studies.

Published
2016

5. The Allograft Inflammatory Factor-1 (AIF-1) homologous in Hirudo medicinalis (medicinal leech) is involved in immune response during wound healing and graft rejection processes

Author

T Schorn, F Drago, M de Eguileor, R Valvassori, J Vizioli, G Tettamanti, and A Grimaldi

Subjects
leech, CD45, AIF-1, wounds, grafts, Biology (General), QH301-705.5
Abstract

Allograft inflammatory factor-1 (AIF-1) is a 17 kDa cytokine-inducible calcium-binding protein that in Vertebrates plays an important role in allografts immune response. Since its expression is mainly limited to the monocyte/macrophage lineage, it was recently suggested that it could play a key role during inflammatory responses, allograft rejection, as well as in the activation of macrophages. To clarify this point we have focused our research on the possible role of AIF-1 during the inflammatory response after injury in the leech Hirudo medicinalis (Annelida, Hirudinea). This invertebrate is an excellent animal model since the responses evoked during inflammation and tissue repair are clear and easily detectable and have a striking similarity with vertebrate responses. Moreover the analysis of an EST library from H. medicinalis CNS, revealed the presence of a gene, named Hmaif-1/alias Hmiba1, showing a high homology with vertebrate aif-1. Our data show that the related protein, named HmAIF-1, is constitutively expressed in unlesioned leeches and that dramatically increases 48 h after wounds and tissue transplants. Immunohistochemistry experiments, using a specific anti HmAIF-1 polyclonal antibody, shows that this factor is present in spread, CD68+ /CD45+ macrophage-like cells. A few days after experimental wounding of the body wall, the amount of these immunopositive cells increases at the lesion site. In conclusion here we propose that in leech HmAIF-1 factor is involved in inflammation events like its vertebrate counterparts.

Published
2015

6. Functional amyloid formation in LPS activated cells from invertebrates to vertebrates

Author

A Grimaldi, G Tettamanti, R Girardello, L Pulze, R Valvassori, D Malagoli, E Ottaviani, and M de Eguileor

Subjects
LPS, amyloid fibrils, ROS, ACTH axis, Biology (General), QH301-705.5
Abstract

LPS stimulation provokes serious cellular stress with an increase of cytoplasmic reactive oxygen species (ROS). We have investigated, among the different cellular defenses, amyloidogenesis as common physiological response to attenuate oxidative stress. Optical and electron microscopic observations of the following LPS activated cell lines [insect (larval hemocytes, IPLB-LdFB and Drosophila Schneider’s S2 cells); mouse (NIH3T3 embryonic fibroblasts); Human (Human Umbilical Vein Endothelial Cells (HUVEC), neutrophils, and mesenchymal stem cells] reveal that, all are characterized by irregular profiles, cytoplasmic empty vacuoles or by cisternae containing fibrillar material. The compartmentalized fibrillar material shows staining properties typical of amyloid fibrils. LPS activation leads to ROS generation, resulting in pH acidification. Stimulated cells show pink cytoplasm in May-Grünwald Giemsa differential staining, giving a gross indication of a lower intracellular pH. Moreover the activation of amyloidogenesis is also linked with an extensive production of ACTH and α-MSH in all cultured cell types. We suggest that amyloidogenesis is a common, physiological cellular response to weak ROS, starting when other anti-stress cellular systems failed to restore homeostasis. The morphological evidence and/or functional characterization of synthesized amyloid fibrils could be an early indicator of oxidative stress that may lead to a general inflammatory process.

Published
2014

7. Ras activation in Hirudo medicinalis angiogenic process

Author

R Valvassori, G Tettamanti, R Ferrarese, A Grimaldi, and M de Eguileor

Subjects
leech, Ras, cytoskeleton, angiogenesis, Biology (General), QH301-705.5
Abstract

In some leeches like Hirudo medicinalis, any kind of stimulation (surgical wound or growth factor injection) provokes the botryoidal tissue response. This peculiar tissue, localized in the loose connective tissue between gut and body wall, is formed by granular botryoidal cells and flattened endothelial-like cells. Under stimulation, the botryoidal tissue changes its shape to form new capillaries. In mammals, the molecular regulation of the angiogenic phenotype requires coordinated input from a number of signalling molecules: among them the GTPase Ras is one of the major actor. In our current study, we determine whether Ras activation alone would be sufficient to drive vessels formation from leech botryoidal tissue. Our findings indicate that assembly and disassembly of actin filaments regulated by Ras protein is involved in morphological modification of botryoidal tissue cells during leech angiogenic process.

Published
2013

8. Amyloid/Melanin distinctive mark in invertebrate immunity

Author

A Grimaldi, R Girardello, D Malagoli, P Falabella, G Tettamanti, R Valvassori, E Ottaviani, and M de Eguileor

Subjects
amyloid fibrils, melanin, ACTH, α-MSH, neutral endopeptidase, invertebrate immunity, Biology (General), QH301-705.5
Abstract

Protostomes and Deuterostomes show the same nexus between melanin production, and amyloid fibril production, i.e., the presence of melanin is indissolubly linked to amyloid scaffold that, in turn, is conditioned by the redox status/cytoplasmic pH modification, pro-protein cleavage presence, adrenocorticotropin hormone (ACTH), melanocyte-stimulating hormone (α-MSH), and neutral endopeptidase (NEP) overexpressions. These events represent the crucial component of immune response in invertebrates, while in vertebrates these series of occurrences could be interpreted as a modest and very restricted innate immune response. On the whole, it emerges that the mechanisms involving amyloid fibrils/pigment synthesis in phylogenetically distant metazoan (viz, cnidaria, molluscs, annelids, insects, ascidians and vertebrates) are evolutionary conserved. Furthermore, our data show the relationship between immune and neuroendocrine systems in amyloid/melanin synthesis. Indeed the process is closely associated to ACTH-α-MSH production, and their role in stress responses leading to pigment production reflects and confirms again their ancient phylogeny.

Published
2012

9. Autophagy in Lepidoptera: more than old wine in new bottle

Author

G Tettamanti, Y Cao, Q Feng, A Grimaldi, and M de Eguileor

Subjects
autophagy, Lepidoptera, Bombyx mori, ATG genes, apoptosis, Biology (General), QH301-705.5
Abstract

Autophagy is a cellular pathway that leads to the degradation of proteins and organelles. This process is usually involved in the maintenance of cell homeostasis when the organism experiences nutrient starvation, but in holometabolous insects autophagy also intervenes in the demolition of larval tissues and organs during metamorphosis. This review summarizes the current knowledge about autophagy research in Lepidoptera and discusses the use of moths and butterflies as models for tudying the roles and regulation of autophagy. It also gives insights into the cooperation between utophagy and apoptosis in cell death events that occur in lepidopteran in vivo and in vitro systems.

Published
2011

11. A hedgehog-like signal is involved in slow muscle differentation in Sepia officinalis

Author

A Grimaldi, G Tettamanti, ML Guidali, MF Brivio, R Valvassori, and M de Eguilor

Subjects
development, helical and cross-striated fibres, mollusc, muscle differentiation, Hh-like protein, Biology (General), QH301-705.5
Abstract

In the tentacle of Sepia officinalis, smooth-like, helical and cross-striated fibres deriving from different populations of myoblasts are present. Myoblasts appear at different times during the development and express two muscle-specific transcription factors: Myf5-like and MyoD-like factors. Myoblasts expressing Myf5 give rise to slow fibres, whereas fast fibres derive from MyoD+ myoblasts. We found that a Hedgehog (Hh)-like signal was present in the central nerve cord of the tentacle from the early stages of development and in a specific population of myoblasts which are the precursors of slow muscle fibres. The model showed interesting similarities with vertebrates, in which Sonic hedgehog is a protein secreted by axial structures (the notochord and neurotube) and is involved in slow muscle differentiation and in survival of muscle precursors.

Published
2007

12. Early suppression of immune response in Heliothis virescens larvae by the endophagous

Author

R Ferrarese, M Brivio, T Congiu, P Falabella, A Grimaldi, M Mastore, G Perletti, F Pennacchio, L Sciacca, G Tettamanti, R Valvassori, and M de Eguileor

Subjects
insects, parasitoid, immune defenses, Biology (General), QH301-705.5
Abstract

Toxoneuron nigriceps is an endophagous parasitoid of larval stages of the noctuid moth Heliothisvirescens. As all parasitoids, this wasp avoid host immune reaction by a combination of several passiveand active mechanisms. Secretions injected by ovipositing females, which contain venom, calyx fluid andpolydnaviruses, are the most probably factors actively disrupting Heliothis virescens immune system. Thispaper describes the main alterations of the host immune response observed shortly after oviposition by T.nigriceps. A transient block of prophenoloxidase activity is registered along with changes in hemocytenumber, adhesion and structure, which suggest the occurrence of apoptosis. In contrast, the hostplasmatocytes appear structurally unaltered, but unable to produce a capsule in vitro.

Published
2005

13. Role of cathepsin B in leech wound healing

Author

A Grimaldi, G Tettamanti, L Rinaldi, G Perletti, R Valvassori, and M de Eguileor

Subjects
leeches, cathepsin-B, immune cells, angiogenesis, Biology (General), QH301-705.5
Abstract

The wound healing process in leeches involves different types of cells like macrophages, NK-likecells and granulocytes. These cells that are involved in immune defence, can co-operate to attackand/or isolate the non self (de Eguileor et al., 1999; de Eguileor et al., 2000a; de Eguileor et al.,2000b). In addition other types of cells, like fibroblasts and endothelial cells, are involved in theformation of new vessels. To exert their functional role, all these cells must infiltrate and migratethrough extracellular matrix (de Eguileor et al., 2001a; de Eguileor et al., 2003).Here we show, by histochemical and biochemical methods, that the cathepsin B peptidase ispresent and active in all migrating cells, involved in immune responses of leeches subjected todifferent stimuli. Interstingly the cellular function of cathepsin B in invertebrates appear to beequivalent to that of vertebrates, where the secreted enzyme plays a role in basement membrane andmatrix disruption operated by cells involved in angiogenesis, wound repair and immune defence.

Published
2004

14. Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)

Author

D. KLIONSKY, A. ABDEL-AZIZ, S. ABDELFATAH, M. ABDELLATIF, A. ABDOLI, S. ABEL, H. ABELIOVICH, M. ABILDGAARD, Y. ABUDU, A. ACEVEDO-AROZENA, I. ADAMOPOULOS, K. ADELI, T. ADOLPH, A. ADORNETTO, E. AFLAKI, G. AGAM, A. AGARWAL, B. AGGARWAL, M. AGNELLO, P. AGOSTINIS, J. AGREWALA, A. AGROTIS, P. AGUILAR, S. AHMAD, Z. AHMED, U. AHUMADA-CASTRO, S. AITS, S. AIZAWA, Y. AKKOC, T. AKOUMIANAKI, H. AKPINAR, A. AL-ABD, L. AL-AKRA, A. AL-GHARAIBEH, M. ALAOUI-JAMALI, S. ALBERTI, E. ALCOCER-GOMEZ, C. ALESSANDRI, M. ALI, M. AL-BARI, S. ALIWAINI, J. ALIZADEH, E. ALMACELLAS, A. ALMASAN, A. ALONSO, G. ALONSO, N. ALTAN-BONNET, D. ALTIERI, S. ALVES, C. DA COSTA, M. ALZAHARNA, M. AMADIO, C. AMANTINI, C. AMARAL, S. AMBROSIO, A. AMER, V. AMMANATHAN, Z. AN, S. ANDERSEN, S. ANDRABI, M. ANDRADE-SILVA, A. ANDRES, S. ANGELINI, D. ANN, U. ANOZIE, M. ANSARI, P. ANTAS, A. ANTEBI, Z. ANTON, T. ANWAR, L. APETOH, N. APOSTOLOVA, T. ARAKI, Y. ARAKI, K. ARASAKI, W. ARAUJO, J. ARAYA, C. ARDEN, M. AREVALO, S. ARGUELLES, E. ARIAS, J. ARIKKATH, H. ARIMOTO, A. ARIOSA, D. ARMSTRONG-JAMES, L. ARNAUNE-PELLOQUIN, A. AROCA, D. ARROYO, I. ARSOV, R. ARTERO, D. ASARO, M. ASCHNER, M. ASHRAFIZADEH, O. ASHUR-FABIAN, A. ATANASOV, A. AU, P. AUBERGER, H. AUNER, L. AURELIAN, R. AUTELLI, L. AVAGLIANO, Y. AVALOS, S. AVEIC, C. AVELEIRA, T. AVINWITTENBERG, Y. AYDIN, S. AYTON, S. AYYADEVARA, M. AZZOPARDI, M. BABA, J. BACKER, S. BACKUES, D. BAE, O. BAE, S. BAE, E. BAEHRECKE, A. BAEK, S. BAEK, G. BAGETTA, A. BAGNIEWSKA-ZADWORNA, H. BAI, J. BAI, X. BAI, Y. BAI, N. BAIRAGI, S. BAKSI, T. BALBI, C. BALDARI, W. BALDUINI, A. BALLABIO, M. BALLESTER, S. BALAZADEH, R. BALZAN, R. BANDOPADHYAY, S. BANERJEE, Y. BAO, M. BAPTISTA, A. BARACCA, C. BARBATI, A. BARGIELA, D. BARILA, P. BARLOW, S. BARMADA, E. BARREIRO, G. BARRETO, J. BARTEK, B. BARTEL, A. BARTOLOME, G. BARVE, S. BASAGOUDANAVAR, D. BASSHAM, R. JR, A. BASU, H. BATOKO, I. BATTEN, E. BAULIEU, B. BAUMGARNER, J. BAYRY, R. BEALE, I. BEAU, F. BEAUMATIN, L. BECHARA, G. BECK, M. BEERS, J. BEGUN, C. BEHRENDS, G. BEHRENS, R. BEI, E. BEJARANO, S. BEL, C. BEHL, A. BELAID, N. BELGAREH-TOUZE, C. BELLAROSA, F. BELLEUDI, M. PEREZ, R. BELLO-MORALES, J. BELTRAN, S. BELTRAN, D. BENBROOK, M. BENDORIUS, B. BENITEZ, I. BENITO-CUESTA, J. BENSALEM, M. BERCHTOLD, S. BEREZOWSKA, D. BERGAMASCHI, M. BERGAMI, A. BERGMANN, L. BERLIOCCHI, C. BERLIOZ-TORRENT, A. BERNARD, L. BERTHOUX, C. BESIRLI, S. BESTEIRO, V. BETIN, R. BEYAERT, J. BEZBRADICA, K. BHASKAR, I. BHATIA-KISSOVA, R. BHATTACHARYA, S. BHATTACHARYA, S. BHATTACHARYYA, M. BHUIYAN, S. BHUTIA, L. BI, X. BI, T. BIDEN, K. BIJIAN, V. BILLES, N. BINART, C. BINCOLETTO, A. BIRGISDOTTIR, G. BJORKOY, G. BLANCO, A. BLAS-GARCIA, J. BLASIAK, R. BLOMGRAN, K. BLOMGREN, J. BLUM, E. BOADA-ROMERO, M. BOBAN, K. BOESZEBATTAGLIA, P. BOEUF, B. BOLAND, P. BOMONT, P. BONALDO, S. BONAM, L. BONFILI, J. BONIFACINO, B. BOONE, M. BOOTMAN, M. BORDI, C. BORNER, B. BORNHAUSER, G. BORTHAKUR, J. BOSCH, S. BOSE, L. BOTANA, J. BOTAS, C. BOULANGER, M. BOULTON, M. BOURDENX, B. BOURGEOIS, N. BOURKE, G. BOUSQUET, P. BOYA, P. BOZHKOV, L. BOZI, T. BOZKURT, D. BRACKNEY, C. BRANDTS, R. BRAUN, G. BRAUS, R. BRAVO-SAGUA, J. BRAVO-SAN PEDRO, P. BREST, M. BRINGER, A. BRIONES-HERRERA, V. BROADDUS, P. BRODERSEN, E. ALVAREZ, J. BRODSKY, S. BRODY, P. BRONSON, J. BRONSTEIN, C. BROWN, R. BROWN, P. BRUM, J. BRUMELL, N. BRUNETTI-PIERRI, D. BRUNO, R. BRYSON-RICHARDSON, C. BUCCI, C. BUCHRIESER, M. BUENO, L. BUITRAGO-MOLINA, S. BURASCHI, S. BUCH, J. BUCHAN, E. BUCKINGHAM, H. BUDAK, M. BUDINI, G. BULTYNCK, F. BURADA, J. BURGOYNE, M. BURON, V. BUSTOS, S. BUTTNER, E. BUTTURINI, A. BYRD, I. CABAS, S. CABRERA-BENITEZ, K. CADWELL, J. CAI, L. CAI, Q. CAI, M. CAIRO, J. CALBET, G. CALDWELL, K. CALDWELL, J. CALL, R. CALVANI, A. CALVO, M. BARRERA, N. CAMARA, J. CAMONIS, N. CAMOUGRAND, M. CAMPANELLA, E. CAMPBELL, F. CAMPBELL-VALOIS, S. CAMPELLO, I. CAMPESI, J. CAMPOS, O. CAMUZARD, J. CANCINO, D. DE ALMEIDA, L. CANESI, I. CANIGGIA, B. CANONICO, C. CANTI, B. CAO, M. CARAGLIA, B. CARAMES, E. CARCHMAN, E. CARDENAL-MUNOZ, C. CARDENAS, L. CARDENAS, S. CARDOSO, J. CAREW, G. CARLE, G. CARLETON, S. CARLONI, D. CARMONA-GUTIERREZ, L. CARNEIRO, O. CARNEVALI, J. CAROSI, S. CARRA, A. CARRIER, L. CARRIER, B. CARROLL, A. CARTER, A. CARVALHO, M. CASANOVA, C. CASAS, J. CASAS, C. CASSIOLI, E. CASTILLO, K. CASTILLO, S. CASTILLO-LLUVA, F. CASTOLDI, M. CASTORI, A. CASTRO, M. CASTRO-CALDAS, J. CASTRO-HERNANDEZ, S. CASTRO-OBREGON, S. CATZ, C. CAVADAS, F. CAVALIERE, G. CAVALLINI, M. CAVINATO, M. CAYUELA, P. RICA, V. CECARINI, F. CECCONI, M. CECHOWSKA-PASKO, S. CENCI, V. CEPERUELO-MALLAFRE, J. CERQUEIRA, J. CERUTTI, D. CERVIA, V. CETINTAS, S. CETRULLO, H. CHAE, A. CHAGIN, C. CHAI, G. CHAKRABARTI, O. CHAKRABARTI, T. CHAKRABORTY, M. CHAMI, G. CHAMILOS, D. CHAN, E. CHAN, H. CHAN, M. CHAN, Y. CHAN, P. CHANDRA, C. CHANG, H. CHANG, K. CHANG, J. CHAO, T. CHAPMAN, N. CHARLET-BERGUERAND, S. CHATTERJEE, S. CHAUBE, A. CHAUDHARY, S. CHAUHAN, E. CHAUM, F. CHECLER, M. CHEETHAM, C. CHEN, G. CHEN, J. CHEN, L. CHEN, M. CHEN, N. CHEN, Q. CHEN, R. CHEN, S. CHEN, W. CHEN, X. CHEN, Y. CHEN, Z. CHEN, H. CHENG, J. CHENG, S. CHENG, W. CHENG, X. CHENG, Y. CHENG, Z. CHENG, H. CHEONG, J. CHEONG, B. CHERNYAK, S. CHERRY, C. CHEUNG, K. CHEUNG, E. CHEVET, R. CHI, A. CHIANG, F. CHIARADONNA, R. CHIARELLI, M. CHIARIELLO, N. CHICA, S. CHIOCCA, M. CHIONG, S. CHIOU, A. CHIRAMEL, V. CHIURCHIU, D. CHO, S. CHOE, A. CHOI, M. CHOI, K. CHOUDHURY, N. CHOW, C. CHU, J. CHUA, H. CHUNG, K. CHUNG, S. CHUNG, Y. CHUNG, V. CIANFANELLI, I. CIECHOMSKA, M. CIFUENTES, L. CINQUE, S. CIRAK, M. CIRONE, M. CLAGUE, R. CLARKE, E. CLEMENTI, E. COCCIA, P. CODOGNO, E. COHEN, M. COHEN, T. COLASANTI, F. COLASUONNO, R. COLBERT, A. COLELL, N. COLL, M. COLLINS, M. COLOMBO, D. COLON-RAMOS, L. COMBARET, S. COMINCINI, M. COMINETTI, A. CONSIGLIO, A. CONTE, F. CONTI, V. CONTU, M. COOKSON, K. COOMBS, I. COPPENS, M. CORASANITI, D. CORKERY, N. CORDES, K. CORTESE, M. COSTA, S. COSTANTINO, P. COSTELLI, A. COTO-MONTES, P. CRACK, J. CRESPO, A. CRIOLLO, V. CRIPPA, R. CRISTOFANI, T. CSIZMADIA, A. CUADRADO, B. CUI, J. CUI, Y. CUI, E. CULETTO, A. CUMINO, A. CYBULSKY, M. CZAJA, S. CZUCZWAR, S. D'ADAMO, M. D'AMELIO, D. D'ARCANGELO, A. D'LUGOS, G. D'ORAZI, J. DA SILVA, H. DAFSARI, R. DAGDA, Y. DAGDAS, M. DAGLIA, X. DAI, Y. DAI, J. DAL COL, P. DALHAIMER, L. DALLA VALLE, T. DALLENGA, G. DALMASSO, M. DAMME, I. DANDO, N. DANTUMA, A. DARLING, H. DAS, S. DASARATHY, S. DASARI, S. DASH, O. DAUMKE, A. DAUPHINEE, J. DAVIES, V. DAVILA, R. DAVIS, T. DAVIS, S. NAIDU, F. DE AMICIS, K. DE BOSSCHER, F. DE FELICE, L. DE FRANCESCHI, C. DE LEONIBUS, M. BARBOSA, G. DE MEYER, A. DE MILITO, C. DE NUNZIO, C. DE PALMA, M. DE SANTI, C. DE VIRGILIO, D. DE ZIO, J. DEBNATH, B. DEBOSCH, J. DECUYPERE, M. DEEHAN, G. DEFLORIAN, J. DEGREGORI, B. DEHAY, G. DEL RIO, J. DELANEY, L. DELBRIDGE, E. DELORME-AXFORD, M. DELPINO, F. DEMARCHI, V. DEMBITZ, N. DEMERS, H. DENG, Z. DENG, J. DENGJEL, P. DENT, D. DENTON, M. DEPAMPHILIS, C. DER, V. DERETIC, A. 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PALMIERI, G. PALMISANO, C. PALUMBO, F. PAMPALONI, L. PAN, Q. PAN, W. PAN, X. PAN, G. PANASYUK, R. PANDEY, U. PANDEY, V. PANDYA, F. PANENI, S. PANG, E. PANZARINI, D. PAPADEMETRIO, E. PAPALEO, D. PAPINSKI, D. PAPP, E. PARK, H. PARK, J. PARK, S. PARK, A. PAROLA, J. PARYS, A. PASQUIER, B. PASQUIER, J. PASSOS, N. PASTORE, H. PATEL, D. PATSCHAN, S. PATTINGRE, G. PEDRAZA-ALVA, J. PEDRAZA-CHAVERRI, Z. PEDROZO, G. PEI, J. PEI, H. PELED-ZEHAVI, J. PELLEGRINI, J. PELLETIER, M. PENALVA, D. PENG, Y. PENG, F. PENNA, M. PENNUTO, F. PENTIMALLI, C. PEREIRA, G. PEREIRA, L. PEREIRA, L. DE ALMEIDA, N. PERERA, A. PEREZOLIVA, M. PEREZ-PEREZ, P. PERIYASAMY, A. PERL, C. PERROTTA, I. PERROTTA, R. PESTELL, M. PETERSEN, I. PETRACHE, G. PETROVSKI, T. PFIRRMANN, A. PFISTER, J. PHILIPS, H. PI, A. PICCA, A. PICKRELL, S. PICOT, G. PIERANTONI, M. PIERDOMINICI, P. PIERRE, V. PIERREFITE-CARLE, K. PIERZYNOWSKA, F. PIETROCOLA, M. PIETRUCZUK, C. PIGNATA, F. PIMENTELMUINOS, M. PINAR, R. PINHEIRO, R. PINKAS-KRAMARSKI, P. 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TUXWORTH, J. TYLER, E. TYUTEREVA, Y. UCHIYAMA, A. UGUNKLUSEK, H. UHLIG, I. ULASOV, M. UMEKAWA, C. UNGERMANN, R. UNNO, S. URBE, E. URIBE-CARRETERO, S. USTUN, V. UVERSKY, T. VACCARI, M. VACCARO, B. VAHSEN, H. VAKIFAHMETOGLU-NORBERG, R. VALDOR, M. VALENTE, A. VALKO, R. VALLEE, A. VALVERDE, G. VAN DEN BERGHE, S. VAN DER VEEN, L. VAN KAER, J. VAN LOOSDREGT, S. VAN WIJK, W. VANDENBERGHE, I. VANHOREBEEK, M. VANNIER-SANTOS, N. VANNINI, M. VANRELL, C. VANTAGGIATO, G. VARANO, I. VARELA-NIETO, M. VARGA, M. VASCONCELOS, S. VATS, D. VAVVAS, I. VEGANAREDO, S. VEGA-RUBIN-DE-CELIS, G. VELASCO, A. VELAZQUEZ, T. VELLAI, E. VELLENGA, F. VELOTTI, M. VERDIER, P. VERGINIS, I. VERGNE, P. VERKADE, M. VERMA, P. VERSTREKEN, T. VERVLIET, J. VERVOORTS, A. VESSONI, V. VICTOR, M. VIDAL, C. VIDONI, O. VIEIRA, R. VIERSTRA, S. VIGANO, H. VIHINEN, V. VIJAYAN, M. VILA, M. VILAR, J. VILLALBA, A. VILLALOBO, B. VILLAREJO-ZORI, F. VILLARROYA, J. VILLARROYA, O. VINCENT, C. VINDIS, C. VIRET, M. VISCOMI, D. VISNJIC, I. VITALE, D. VOCADLO, O. VOITSEKHOVSKAJA, C. VOLONTE, M. VOLTA, M. VOMERO, C. VON HAEFEN, M. VOOIJS, W. VOOS, L. VUCICEVIC, R. WADE-MARTINS, S. WAGURI, K. WAITE, S. WAKATSUKI, D. WALKER, M. WALKER, S. WALKER, J. WALTER, F. WANDOSELL, B. WANG, C. WANG, D. WANG, F. WANG, G. WANG, H. WANG, J. WANG, K. WANG, L. WANG, M. WANG, N. WANG, P. WANG, Q. WANG, W. WANG, X. WANG, Y. WANG, Z. WANG, G. WARNES, V. WARNSMANN, H. WATADA, E. WATANABE, M. WATCHON, T. WEAVER, G. WEGRZYN, A. WEHMAN, H. WEI, L. WEI, T. WEI, Y. WEI, O. WEIERGRABER, C. WEIHL, G. WEINDL, R. WEISKIRCHEN, A. WELLS, R. WEN, X. WEN, A. WERNER, B. WEYKOPF, S. WHEATLEY, J. WHITTON, A. WHITWORTH, K. WIKTORSKA, M. WILDENBERG, T. WILEMAN, S. WILKINSON, D. WILLBOLD, B. WILLIAMS, R. WILLIAMS, P. WILLIAMSON, R. WILSON, B. WINNER, N. WINSOR, S. WITKIN, H. WODRICH, U. WOEHLBIER, T. WOLLERT, E. WONG, J. WONG, R. WONG, V. WONG, W. WONG, A. WU, C. WU, J. WU, K. WU, M. WU, S. WU, W. WU, X. WU, Y. WU, R. XAVIER, H. XIA, L. XIA, Z. XIA, G. XIANG, J. XIANG, M. XIANG, W. XIANG, B. XIAO, G. XIAO, H. XIAO, J. XIAO, L. XIAO, S. XIAO, Y. XIAO, B. XIE, C. XIE, M. XIE, Y. XIE, Z. XIE, M. XILOURI, C. XU, E. XU, H. XU, J. XU, L. XU, W. XU, X. XU, Y. XUE, S. YAKHINE-DIOP, M. YAMAGUCHI, O. YAMAGUCHI, A. YAMAMOTO, S. YAMASHINA, S. YAN, Z. YAN, Y. YANAGI, C. YANG, D. YANG, H. YANG, J. YANG, L. YANG, M. YANG, P. YANG, Q. YANG, S. YANG, W. YANG, X. YANG, Y. YANG, H. YAO, S. YAO, X. YAO, Y. YAO, T. YASUI, M. YAZDANKHAH, P. YEN, C. YI, X. YIN, Y. YIN, Z. YIN, M. YING, Z. YING, C. YIP, S. YIU, Y. YOO, K. YOSHIDA, S. YOSHII, T. YOSHIMORI, B. YOUSEFI, B. YU, H. YU, J. YU, L. YU, M. YU, S. YU, V. YU, W. YU, Z. YU, J. YUAN, L. YUAN, S. YUAN, Y. YUAN, Z. YUAN, J. YUE, Z. YUE, J. YUN, R. YUNG, D. ZACKS, G. ZAFFAGNINI, V. ZAMBELLI, I. ZANELLA, Q. ZANG, S. ZANIVAN, S. ZAPPAVIGNA, P. ZARAGOZA, K. ZARBALIS, A. ZAREBKOHAN, A. ZARROUK, S. ZEITLIN, J. ZENG, E. ZEROVNIK, L. ZHAN, B. ZHANG, D. ZHANG, H. ZHANG, J. ZHANG, K. ZHANG, L. ZHANG, M. ZHANG, P. ZHANG, S. ZHANG, W. ZHANG, X. ZHANG, Y. ZHANG, Z. ZHANG, H. ZHAO, L. ZHAO, S. ZHAO, T. ZHAO, X. ZHAO, Y. ZHAO, G. ZHENG, K. ZHENG, L. ZHENG, S. ZHENG, X. ZHENG, Y. ZHENG, Z. ZHENG, B. ZHIVOTOVSKY, Q. ZHONG, A. ZHOU, B. ZHOU, C. ZHOU, G. ZHOU, H. ZHOU, J. ZHOU, K. ZHOU, R. ZHOU, X. ZHOU, Y. ZHOU, Z. ZHOU, B. ZHU, C. ZHU, G. ZHU, H. ZHU, W. ZHU, Y. ZHU, H. ZHUANG, X. ZHUANG, K. ZIENTARA-RYTTER, C. ZIMMERMANN, E. ZIVIANI, T. ZOLADEK, W. ZONG, D. ZOROV, A. ZORZANO, W. ZOU, Z. ZOU, S. ZURYN, W. ZWERSCHKE, B. BRAND-SABERI, C. KENCHAPPA, S. OSHIMA, Y. RONG, J. SLUIMER, and C. STALLINGS

Subjects
flux, macroautophagy, phagophore, stress, vacuole, Autophagosome, LC3, lysosome, neurodegeneration, cancer
Abstract

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.

Published
2021

15. Ras activation in Hirudo medicinalis angiogenic process

Author

A Grimaldi, R Ferrarese, G Tettamanti, R Valvassori, and M de Eguileor

Subjects
leech, Ras, cytoskeleton, angiogenesis, Biology (General), QH301-705.5
Abstract

In some leeches like Hirudo medicinalis, any kind of stimulation (surgical wound or growth factor injection) provokes the botryoidal tissue response. This peculiar tissue, localized in the loose connective tissue between gut and body wall, is formed by granular botryoidal cells and flattened endothelial-like cells. Under stimulation, the botryoidal tissue changes its shape to form new capillaries. In mammals, the molecular regulation of the angiogenic phenotype requires coordinated input from a number of signalling molecules: among them the GTPase Ras is one of the major actor. In our current study, we determine whether Ras activation alone would be sufficient to drive vessels formation from leech botryoidal tissue. Our findings indicate that assembly and disassembly of actin filaments regulated by Ras protein is involved in morphological modification of botryoidal tissue cells during leech angiogenic process.

Published
2013

16. Autophagy in Lepidoptera: more than old wine in new bottle

Author

G Tettamanti, Y Cao, Q Feng, A Grimaldi, and M de Eguileor

Subjects
autophagy, Lepidoptera, Bombyx mori, ATG genes, apoptosis, Biology (General), QH301-705.5
Abstract

Autophagy is a cellular pathway that leads to the degradation of proteins and organelles. This process is usually involved in the maintenance of cell homeostasis when the organism experiences nutrient starvation, but in holometabolous insects autophagy also intervenes in the demolition of larval tissues and organs during metamorphosis. This review summarizes the current knowledge about autophagy research in Lepidoptera and discusses the use of moths and butterflies as models for studying the roles and regulation of autophagy. It also gives insights into the cooperation between autophagy and apoptosis in cell death events that occur in lepidopteran in vivo and in vitro systems.

Published
2010

17. Preparation of lyso-GM1 (II3Neu5AcGgOse4-long chain bases) by a one-pot reaction.

Author

S Sonnino, D Acquotti, G Kirschner, A Uguaglianza, L Zecca, F Rubino, and G Tettamanti

Subjects
Biochemistry, QD415-436
Abstract

A simple procedure is described for preparing lyso-GM1, a GM1 derivative that lacks the fatty acid moiety, starting from GM1 ganglioside using a one-pot reaction. Ganglioside deacylation was carried out in KOH/propan-1-ol in the absence of oxygen. The yield of lyso-GM1 under optimal conditions (6 h, 90 degrees C, 0.2 N KOH, 1 mM GM1) was 54%. The chemical structure of lyso-GM1 was determined by 1H-NMR and FAB-MS analyses, thus proving that the acetamide groups of galactosamine and sialic acid units were not affected during the deacylation reaction.

Published
1992
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19. Chemistry of the Mucins1

Author

G. Tettamanti and W. Pigman

Subjects
Pathology, medicine.medical_specialty, Chemistry, medicine, Chemistry (relationship), medicine.disease, Cystic fibrosis
Published
2015
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20. Gangliosides and Neuronal Plasticity

Author

G. Tettamanti, Robert Ledeen, K. Sandhoff, Y. Nagai, G. Toffano, G. Tettamanti, Robert Ledeen, K. Sandhoff, Y. Nagai, and G. Toffano

Subjects
Neurosciences, Cytology, Biochemistry
Abstract

This volume contains the Proceedings of the Meeting'Neuronal plasticity and gangliosides'which was held at Mantova, Italy, on May 29-31, 1985, as a satellite to the Tenth Meeting of the International Society for Neurochemistry, (Riva del Garda, Italy, May 19-24,1985). The Symposium took place in the'Teatro Bibiena', one of the oldest and most beautiful theatres in Italy, known for having been the place for some of the very first performances of W.A. Mozart. The number of registered participants in the Meeting was about 180 including 40 accor:Qpanying persons. The persons invited as Speakers or Chairmen of Colloquia and Workshops were 48. Eighteen countries were represented with the largest contingent coming from Italy, followed by Federal Republic of Germany, The United States, France and Great Britain. The Meeting was based on Colloquia, Workshops, Round Tables and Poster Sessions, with a total of 42 Lectures and 32 Poster presentations.

Published
2013

21. Preparation of GM1 ganglioside molecular species having homogeneous fatty acid and long chain base moieties.

Author

S Sonnino, G Kirschner, R Ghidoni, D Acquotti, and G Tettamanti

Subjects
Biochemistry, QD415-436
Abstract

A new procedure is described for preparing the molecular species of GM1 ganglioside that carry a single fatty acid (myristic (C14:0), stearic (C18:0), arachidic (C20:0) or lignoceric (C24:0) acid) and a single long chain base (C18 or C20 sphingosine, C18 or C20 sphinganine, each of them in natural 3D(+)erythro or unnatural 3L(-)threo form). The procedure consisted of the following steps: a) alkaline hydrolysis of GM1 ganglioside in the presence of tetramethylammonium hydroxide, which produces de-N-acylation of the ceramide and de-N-acetylation of the sialic acid residue; b) specific re-N-acylation at the long chain base amino group with a new fatty acid (myristic, stearic, arachidic, or lignoceric) in the presence of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride; and c) final re-N-acetylation at the level of the sialic acid residue. GM1 ganglioside molecular species, completely homogeneous in the ceramide portion, were prepared by reversed phase high performance liquid chromatography. The GM1 ganglioside molecular species were analyzed for saccharide, fatty acid, and long chain base composition by chemical and spectrometric analyses. Using a combination of the two procedures, 32 different molecular species of GM1 ganglioside, over 99% homogeneous, have been prepared.

Published
1985
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22. Specific tritium labeling of gangliosides at the 3-position of sphingosines.

Author

R Ghidoni, S Sonnino, M Masserini, P Orlando, and G Tettamanti

Subjects
Biochemistry, QD415-436
Abstract

GM1 and GD1a gangliosides, treated with 2,3-dichloro-5,6-dicyano benzoquinone (DDQ) in the presence of Triton X-100 and in a toluene medium were specifically oxidized at the 3-position of sphingosine. The maximum reaction yield (65%) was obtained after 40 hours at 37 degrees C with the following molar ratio of reactants: ganglioside-Triton X-100-DDQ 1:70:125. The formation of the 3-keto derivatives of GM1 and GD1a was demonstrated by: a) the appearance of a sharp peak at 1700 cm-1 and of a broad band at 1250 cm-1 (typical of allylic ketones and of carbonyl groups, respectively) in the infra-red spectrum; b) the appearance of an absorption maximum at 230 nm, identical to that featured by 3-keto-cerebrosides, in the ultraviolet spectrum; c) the degradation of long chain bases during the process of release from gangliosides and derivatization for analysis by gas-liquid chromatography (expected for long chain bases carrying a keto group in the 3-position); and d) the quantitative transformation of 3-keto-GM1 and 3-keto-GD1a to GM1 and GD1a, respectively, upon NaBH4 reduction. Reduction of 3-keto-GM1 and 3-keto-GD1a with [3H]-NaBH4 produced 3H-labeled GM1 and GD1a. [3H]GM1 and [3H]GD1a maintained the same carbohydrate and fatty acid composition of the original GM1 and GD1a, and did not contain any saturated long chain bases. Direct proof that the label was at C-3 of long chain bases was given by reoxidation with DDQ, which completely removed the label, and by ozonolysis, after which label was retained on the oligosaccharide-containing fragment. More than 99% of incorporated radioactivity was carried by the long chain bases. The radiochemical purity of labeled gangliosides was greater than 95% and the specific radioactivity was 1.25 and 1.28 Ci/m mol for [3H]GM1 and [3H]GD1a, respectively.

Published
1981
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23. High performance liquid chromatography preparation of the molecular species of GM1 and GD1a gangliosides with homogeneous long chain base composition.

Author

S Sonnino, R Ghidoni, G Gazzotti, G Kirschner, G Galli, and G Tettamanti

Subjects
Biochemistry, QD415-436
Abstract

A semi-preparative, analytical high performance liquid chromatographic (HPLC) procedure is described for the isolation of molecular species of GM1 and GD1a gangliosides containing a single long chain base, C18 or C20 sphingosine, C18 or C20 sphinganine, each in its natural erythro or unnatural threo form. The threo forms were obtained from 2,3-dichloro-5,6-dicyanobenzoquinone/NaBH4 -treated gangliosides. The ganglioside molecular species separated by HPLC were analyzed for carbohydrate, fatty acid, and long chain base composition. In particular, long chain bases were submitted to gas-liquid chromatographic-mass spectrometric analyses as their trimethylsilyl (TMS) or N-acetyl-TMS derivatives, and chain length, presence or absence of C4-C5 double bond, and C-3 steric configuration were ascertained. The final preparations of individual molecular species of GM1 and GD1a gangliosides were more than 99% homogeneous in their saccharide moiety, contained a single long chain base (homogeneity higher than 99%), and had a fatty acid composition primarily of stearic acid (92 to 97%). All the individual molecular species of GM1 and GD1a gangliosides were also prepared in radioactive form by selective tritiation at C-3 of the long chain base. Their specific radioactivity ranged from 1.3 to 1.45 Ci/mmol. The availability of these molecular species of gangliosides is expected to facilitate studies aimed at ascertaining the role played by the hydrophobic portion in the functional behavior of gangliosides.

Published
1984
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25. triggers megakaryocytic differentiation in chronic myeloid leukemic cells, K562, through the increase if ganglioside GM3 content

Author

B. Lupo, C. Tringali, F. Cirillo, N. Papini, L. Anastasia, E. Monti, G. Tettamanti, B. Venerando, Lupo, B., Tringali, C., Cirillo, F., Papini, N., Anastasia, L., Monti, E., Tettamanti, G., and Venerando, B.

Abstract

Chronic myeloid leukaemia (CML) is a paradigmatic example of neoplasia in which a differentiation arrest occurs during the myeloid lineage and a highly proliferative malignant clone originates1. In the context of cancer disease and differentiation, an ever-increasing interest is being focused on sialidases and sialoglycoconjugates since alterations in these fields are directly interconnected to neoplastic transformation2. In particular, the plasma-membrane associated sialidase Neu3 over-expression, reported in several tumours, is linked to apoptosis resistance phenomena. In this report, we demonstrated that the silencing of Neu3 in the CML K562 cells decreases proliferation rate and apoptosis resistance in favour of a differentiation process. K562 cells were transduced with a shRNA targeting the coding region of Neu3, inserted in a lentiviral vector. Neu3 silencing (-70 % as protein content and – 93 %, as catalytic activity) gave rise to significant events. First of all, cyclin D2 and Myc were much less expressed (- 40 % and – 30 %, respectively) while p21 increased (+ 60 %); as consequence, cell growth and [3H]thymidine incorporation (- 47 %) diminished. Apoptosis resistance toward chemotherapeutic molecules such as etoposide and staurosporine decreased, accordingly to a concurrent decrease of the anti-apoptotic protein Bcl2 (- 30 %) and to an increase of the pro-apoptotic proteins Bax and Bad (+ 17 % and + 32 %, respectively). Moreover, K562 cells became able to differentiate toward the megakaryocytic lineage as proved by the appearance of the megakaryocytic markers CD10, CD44, CD41, CD61. This important cascade of events was triggered by the activation of the signalling pathways PLC-b2, PKC, RAF, ERK1/2, RSK90, and JNK. The molecular connection between Neu3 silencing and the activation of PLC-b2 has to be searched in the significant increase of GM3 (+ 81 %), as demonstrated by the treatment of K562 cells with brefeldin A which simulated a GM3-rich conformation. Therefore, these results indicate that Neu3 plays a decisive role in CML and could be an interesting target for developing therapeutic strategies.

Published
2008

29. Valutazione dell'espressione dell'RNA messaggero di troponina T cardiaca e beta-miosina in cellule staminali mesenchimali esposte a condizioni di differenziamento in vitro

Author

F. Macini, M. Carboni, L. Anastasia, N. Papini, G. Tettamanti, B. Venerando, BONAFÈ, FRANCESCA, FIUMANA, EMANUELA, MUSCARI, CLAUDIO, CALDARERA, CLAUDIO MARCELLO, GUARNIERI, CARLO, F.Macini, M.Carboni, F.Bonafè, E.Fiumana, L.Anastasia, N.Papini, G.Tettamanti, B.Venerando, C.Muscari, C.M.Caldarera, and C.Guarnieri

Published
2006

33. Hirudo medicinalis: a new model for testing activators and inhibitors of angiogenesis

Author

M, de Eguileor, A, Grimaldi, G, Tettamanti, R, Ferrarese, T, Congiu, M, Protasoni, G, Perletti, R, Valvassori, and G, Lanzavecchia

Subjects
Vascular Endothelial Growth Factor A, Lymphokines, Microscopy, Electron, Vascular Endothelial Growth Factors, Leeches, Models, Animal, Animals, Granulocyte-Macrophage Colony-Stimulating Factor, Angiogenesis Inhibitors, Fibroblast Growth Factor 2, Endothelial Growth Factors, Immunohistochemistry
Abstract

An increasing body of evidence indicates that in the leech Hirudo medicinalis the angiogenic process is finely regulated and coordinated by the botryoidal tissue. In this paper we provide evidence on the involvement of botryoidal tissue cells in angiogenesis induced in H. medicinalis by a variety of stimuli including surgical wounds or the administration of modulators of neovascularization. Interestingly, we show that either human activators of vascular cell growth, or anti-angiogenic peptides like angiostatin and endostatin, or the drug mitomycin, can induce a prompt biological response in H. medicinalis. We show as well that angiogenesis in this invertebrate shares a surprising degree of similarity with neovascularization in vertebrates, both at the biochemical and cellular levels, because it involves similar growth factors/growth factor receptors, and relies on analogous cell-cell or cell-matrix interactions. For these reasons we suggest that H. medicinalis can be used as a reproducible model for testing activators or inhibitors of angiogenesis, and for investigating the biochemical, ultrastructural and cellular processes involved in new vessel formation.

Published
2002

34. Different behavior of ghost-linked acidic and neutral sialidases during human erythrocyte ageing

Author

C, Tringali, A, Fiorilli, B, Venerando, and G, Tettamanti

Subjects
Adult, Male, Phosphatidylinositol Diacylglycerol-Lyase, Type C Phospholipases, Erythrocyte Membrane, Humans, Membrane Proteins, Neuraminidase, Female, Erythrocyte Aging, Hydrogen-Ion Concentration
Abstract

Acidic and neutral sialidases (pH optimum 4.7 and 7.2, respectively) were assayed on human circulating erythrocytes during ageing. The assays were performed on intact erythrocytes and resealed erythrocyte ghost membranes. From young to senescent erythrocytes the acidic sialidase featured a 2.7-fold and 2.5-fold decrease in specific activity when measured on intact cells or resealed ghost membranes, whereas the neutral sialidase a 5-fold and 7-fold increase, respectively. The Ca2+-loading procedure was employed to mimic the vesiculation process occurring during erythrocyte ageing. Under these conditions the released vesicles displayed an elevated content of acidic sialidase, almost completely linked through a glycan phosphoinositide (GPI) anchor but no neutral sialidase activity, that was completely retained by remnant erythrocytes together with almost all the starting content of sialoglycoconjugates. The loss with vesiculation of acidic sialidase with a concomitant relative increase of neutral sialidase was more marked in young than senescent erythrocytes. The data presented suggest that during ageing erythrocytes loose acidic sialidase, and get enriched in the neutral enzyme, the vesiculation process, possibly involving GPI-anchors-rich membrane microdomains, being likely responsible for these changes. The enhanced neutral sialidase activity might account for the sialic acid loss occurring during erythrocyte ageing.

Published
2002

35. Basic fibroblast growth factor-induced proliferation of primary astrocytes. evidence for the involvement of sphingomyelin biosynthesis

Author

L, Riboni, P, Viani, R, Bassi, P, Giussani, and G, Tettamanti

Subjects
Brefeldin A, Transferases (Other Substituted Phosphate Groups), Ceramides, Tritium, Rats, Sphingomyelins, Enzyme Activation, Animals, Newborn, Sphingosine, Astrocytes, Cerebellum, Serine, Animals, Fibroblast Growth Factor 2, Protein Processing, Post-Translational, Cell Division, Cells, Cultured
Abstract

We recently reported that the marked decrease in cellular ceramide in primary astrocytes is an early event associated with the mitogenic activity of basic fibroblast growth factor (bFGF) (Riboni, L., Viani, P., Bassi, R., Stabieini, A., and Tettamanti, G. (2000) GLIA 32, 137-145). Here we show that a rapid activation of sphingomyelin biosynthesis appears to be the major mechanism responsible for the fall in ceramide levels induced by bFGF. When quiescent astrocytes were treated with bFGF, an increased amount of newly synthesized ceramide (from either l-[(3)H]serine or [(3)H]sphingosine) was directed toward the biosynthesis of sphingomyelin. Conversely, bFGF did not appear to affect ceramide levels by other metabolic pathways involved in ceramide turnover such as sphingomyelin degradation and ceramide biosynthesis, degradation, and glucosylation. Enzymatic studies demonstrating a relevant and rapid increase in sphingomyelin synthase activity after bFGF treatment have provided a convincing explanation for the activation of sphingomyelin biosynthesis. The bFGF-induced increase in sphingomyelin synthase appears to depend on a post-translational activation mechanism. Moreover, in the presence of brefeldin A, the activation of sphingomyelin biosynthesis was abolished, suggesting that the enzyme is located in a compartment other than the Golgi apparatus. Also the phosphatidylcholine-specific phospholipase C inhibitor D609 exerted a potent inhibitory effect on sphingomyelin biosynthesis. Finally, we demonstrate that inhibition of sphingomyelin biosynthesis by brefeldin A or D609 led to a significant inhibition of bFGF-stimulated mitogenesis. All this supports that, in primary astrocytes, the early activation of sphingomyelin synthase is involved in the bFGF signaling pathway leading to proliferation.

Published
2001

36. Association of Src-family protein tyrosine kinases with sphingolipids in rat cerebellar granule cells differentiated in culture

Author

A, Prinetti, N, Marano, S, Prioni, V, Chigorno, L, Mauri, R, Casellato, G, Tettamanti, and S, Sonnino

Subjects
Sphingolipids, Cell Membrane, Molecular Sequence Data, Membrane Proteins, Cell Differentiation, Protein-Tyrosine Kinases, Precipitin Tests, Rats, CSK Tyrosine-Protein Kinase, Rats, Sprague-Dawley, src-Family Kinases, Carbohydrate Sequence, Cerebellum, Gangliosides, Animals, Cells, Cultured
Abstract

Src family kinases play a relevant role in the development and differentiation of neuronal cells. They are abundant in sphingolipid-enriched membrane domains of many cell types, and these domains are hypothesized to function in bringing together molecules important to signal transduction. We studied the association of Src family tyrosine kinases and their negative regulatory kinase, Csk, with sphingolipids in sphingolipid-enriched domains of rat cerebellar granule cells differentiated in culture. We find that c-Src, Lyn and Csk are enriched in the sphingolipid-enriched fraction prepared from these cells. Coimmunoprecipitation experiments show that these and sphingolipids are part of the same domain. Cross-linking experiments with a photoactivable, radioactive GD1b derivative show that c-Src and Lyn, which are anchored to the membrane via a myristoyl chain, associate directly with GD1b. Csk, which is not inserted in the hydrophobic core of the membrane, is not photolabeled by this ganglioside. These results suggest that lipid-lipid, lipid-protein, and protein-protein interactions cooperate to maintain domain structure. We hypothesize that such interactions might play a role in the process of neuronal differentiation.

Published
2001

37. Identification and expression of NEU3, a novel human sialidase associated to the plasma membrane

Author

E, Monti, M T, Bassi, N, Papini, M, Riboni, M, Manzoni, B, Venerando, G, Croci, A, Preti, A, Ballabio, G, Tettamanti, and G, Borsani

Subjects
DNA, Complementary, Blotting, Western, Lipid Bilayers, Molecular Sequence Data, Neuraminidase, Transfection, Gangliosides, Animals, Humans, Tissue Distribution, Amino Acid Sequence, Cloning, Molecular, Gene Library, Expressed Sequence Tags, Base Sequence, Models, Genetic, Chromosomes, Human, Pair 11, Cell Membrane, Sequence Analysis, DNA, Hydrogen-Ion Concentration, Blotting, Northern, Alternative Splicing, Kinetics, Spectrometry, Fluorescence, Microscopy, Fluorescence, COS Cells, Research Article
Abstract

Several mammalian sialidases have been described so far, suggesting the existence of numerous polypeptides with different tissue distributions, subcellular localizations and substrate specificities. Among these enzymes, plasma-membrane-associated sialidase(s) have a pivotal role in modulating the ganglioside content of the lipid bilayer, suggesting their involvement in the complex mechanisms governing cell-surface biological functions. Here we describe the identification and expression of a human plasma-membrane-associated sialidase, NEU3, isolated starting from an expressed sequence tag (EST) clone. The cDNA for this sialidase encodes a 428-residue protein containing a putative transmembrane helix, a YRIP (single-letter amino acid codes) motif and three Asp boxes characteristic of sialidases. The polypeptide shows high sequence identity (78%) with the membrane-associated sialidase recently purified and cloned from Bos taurus. Northern blot analysis showed a wide pattern of expression of the gene, in both adult and fetal human tissues. Transient expression in COS7 cells permitted the detection of a sialidase activity with high activity towards ganglioside substrates at a pH optimum of 3.8. Immunofluorescence staining of the transfected COS7 cells demonstrated the protein's localization in the plasma membrane.

Published
2000

38. Sphingolipid-enriched membrane domains from rat cerebellar granule cells differentiated in culture. A compositional study

Author

A, Prinetti, V, Chigorno, G, Tettamanti, and S, Sonnino

Subjects
Sphingolipids, Cell Membrane, Cell Differentiation, Cytoplasmic Granules, Phosphates, Rats, Rats, Sprague-Dawley, Methionine, Sphingosine, Cerebellum, Animals, Electrophoresis, Polyacrylamide Gel, Chromatography, Thin Layer, Cells, Cultured
Abstract

Sphingolipid-enriched membrane domains, characterized by a particular protein and lipid composition, have been detected in a variety of cells. However, limited data are available concerning these domains in neuronal cells. We analyzed the lipid and protein composition of a sphingolipid-enriched membrane fraction prepared from primary rat cerebellar granule cells differentiated in culture. Although the protein content of this fraction was only 1.4% of total cellular protein, 60% of the gangliosides, 67% of the sphingomyelin, 50% of the ceramide, and 40% of the cholesterol were located in this fraction. The protein pattern of the sphingolipid-enriched domain fraction was dramatically different from that associated with the cell homogenate. This fraction contained 25% of the tyrosine-phosphorylated proteins and was enriched in two proteins with apparent molecular masses of 135 and 15 kDa. 12% of cellular glycerophospholipids were located in the fraction, with phosphatidylcholine having the highest enrichment. The molar ratio between proteins, glycerophospholipids, cholesterol, sphingomyelin, ceramide and gangliosides in cerebellar granule cells was 1.6:41.6:6. 1:1.3:0.3:1 in the cell homogenate and 0.04:8.3:4.0:1.4:0.2:1 in the sphingolipid-enriched membrane fraction. These data indicate that selected proteins segregate with sphingolipids in specialized domains in the membrane of cultured neurons.

Published
2000

42. Histopathological changes after induced injury in leeches

Author

M, de Eguileor, G, Tettamanti, A, Grimaldi, A, Boselli, G, Scarì, R, Valvassori, E L, Cooper, and G, Lanzavecchia

Subjects
Inflammation, Killer Cells, Natural, Wound Healing, Cell Movement, Histocytochemistry, Leeches, Macrophages, Animals, Granulocytes
Abstract

Cells involved in leech inflammatory responses have been characterized by morphological, histochemical, and immunohistochemical methods. Macrophage-like cells, NK-like cells, and granulocytes migrated shortly after injury by pricking with bacterial lipopolysaccharide. Inflammatory responses increased progressively and provoked cell migration to the body wall and then to wound surfaces. Macrophages, NK cells, and granulocytes display similar features and behavior traits in invertebrates and vertebrates.

Published
1999

43. Metabolic processing of gangliosides by normal and Salla human fibroblasts in culture. A study performed by administering radioactive GM3 ganglioside

Author

V, Chigorno, G, Tettamanti, and S, Sonnino

Subjects
Male, Adolescent, Sialoglycoproteins, Proteins, DNA, Fibroblasts, N-Acetylneuraminic Acid, Sphingomyelins, Lysosomal Storage Diseases, Gangliosides, Sialic Acids, Animals, G(M3) Ganglioside, Humans, Cattle, Child, Cells, Cultured
Abstract

Cultured fibroblasts from normal subjects and from subjects affected by Salla disease, characterized by the lack or misfunction of the membrane carrier responsible for the egress of sialic acid from lysosomes, were fed with ganglioside GM3 labeled at the sialic acid acetyl group, [Neu5Ac-3H]GM3, or at C-3 of sphingosine (Sph), [Sph-3H]GM3, or at C-1 of stearoyl chain, [stearoyl-14C]GM3. After a 15-h pulse the total amount of cell-bound GM3 corresponded to about 2% of the endogenous ganglioside content. Cells were then subjected to a 72-h chase, and the radioactive products from both ganglioside catabolism and salvage processes of catabolic fragments were measured. These data indicated that about 50% of the cell-bound ganglioside underwent metabolic processing, suggesting a ganglioside half-life of 2-3 days. [Neu5Ac-3H] formed from [Neu5Ac-3H]GM3 degradation was mostly re-cycled for the biosynthesis of gangliosides and sialoglycoproteins, only a minor part being degraded to [3H]water, which constituted only 1.6% of total metabolite linked radioactivity. [Sph-3H] from the [Sph-3H]GM3 degradation was partly re-cycled for the biosynthesis of gangliosides, neutral glycosphingolipids and sphingomyelin, and partly (about 20% of the total metabolite linked radioactivity) degraded to [3H]water. In Salla fibroblasts metabolic processing of [Neu5Ac-3H]GM3 produced large amounts of free [3H]Neu5Ac, and a reduced incorporation of radioactivity into glycoconjugates (as compared to normal cells). However, the accumulation of free Neu5Ac was not accompanied by an increase of tritiated water. LacCer and Cer from [stearoyl-14C]GM3 catabolism were found to accumulate in Salla fibroblasts, an indication that the enzymes of glycosphingolipid metabolism were affected by the impairment of Neu5Ac egress from lysosomes. Particularly relevant was the accumulation of ceramide which was hardly detectable in control cells.

Published
1996

44. Fluorescence excimer formation imaging: a new technique to investigate association to cells and membrane behavior of glycolipids

Author

A, Terzaghi, G, Tettamanti, P, Palestini, D, Acquotti, G, Bottiroli, and M, Masserini

Subjects
Rats, Sprague-Dawley, Membrane Lipids, Microscopy, Video, Pyrenes, Microscopy, Fluorescence, Image Processing, Computer-Assisted, Animals, G(M1) Ganglioside, Glycolipids, Cells, Cultured, Rats
Abstract

A new fluorescence ratio imaging technique aiming to monitor the lateral distribution of pyrene-labeled lipids in the membranes through visualization of the excimer/monomer (E/M) intensity ratio, has been set up, studying the association of a fluorescent derivative of GM1 ganglioside (pyreneGM1) to rat cerebellar granule cells in culture. The imaging results show that the mean E/M ratio value, under experimental conditions leading to the association of pyreneGM1 with the plasma membrane, is significantly higher in neuritic processes than in cell bodies and, moreover, locally distributed in patches. Fluorescence antisotropy imaging of the fluorescent probe TMA-DPH (trimethylaminodiphenylhexatriene) shows the presence of domains having different fluidity and that the average fluidity is higher in cell bodies than in neuritic processes. Additional experiments using TMA-DPH as a marker of fluid-phase pinocytosis, suggest that the rate of endocytosis is comparable in the two regions of the cell. Taken together, on the one hand these data indicate that the fluorescent ganglioside is present in a more clustered state at the level of neuritic processes than in cell bodies and locally distributed in patches of different size and enrichment. On the other hand, they point out the potentiality of the excimer formation imaging technique to study membrane behavior and dynamics of pyrene-labeled lipids, with a particular insight into their aggregative properties.

Published
1994

46. The lysosomal N-acetyl-beta-D-glucosaminidase (NAG) isoenzymes in plasma: study of distribution in a general population by a simple routine chromatofocusing procedure

Author

G, Goi, C, Bairati, C, Roggi, L, Maccarini, G, Tettamanti, C, Meloni, and A, Lombardo

Subjects
Adult, Male, Chromatography, Alcohol Drinking, Population, Age Factors, Middle Aged, Body Mass Index, Isoenzymes, Sex Factors, Acetylglucosaminidase, Humans, Female, Lysosomes, Aged
Abstract

We have adapted for routine analysis a pre-existing method for separating the three major N-acetyl-beta-D-glucosaminidase (NAG) isoenzyme forms--A, B+I1 and I2--by chromatofocusing followed by fluorimetric assay of the enzyme activity. This method combines good resolution, accurate quantification of the different isoenzymes and high reproducibility with an acceptable degree of analytical precision. We have applied it to studying the isoenzyme levels in the plasma of a general population of 417 subjects and have analysed these enzyme activities as functions of age, sex, body mass and declared alcohol consumption. Unlike the levels of unfractionated enzyme, levels of all the isoenzymes were higher in men than in women at all ages except in the 20-29 year group. Isoenzyme I2 showed the greatest sex difference. On the whole, with increasing age, both sexes showed more or less regular increases in plasma levels of all the isoenzymes. We also found significant correlations for the population as a whole with age and with body mass index. The only significant correlation with alcohol consumption was for B+I1 in men.

Published
1993

47. Gangliosides and neurological diseases

Author

G Doria and G Tettamanti

Subjects
Nervous system, medicine.anatomical_structure, Letter, business.industry, Immunology, General Engineering, General Earth and Planetary Sciences, Medicine, General Medicine, business, Neuroscience, General Environmental Science
Published
1993

49. Relationship between the regulation of membrane enzyme activities by gangliosides and a possible ganglioside segregation in membrane microdomains

Author

S, Sonnino, V, Chigorno, M, Valsecchi, R, Bassi, D, Acquotti, L, Cantu, M, Corti, and G, Tettamanti

Subjects
Carbohydrate Sequence, Gangliosides, Cell Membrane, Molecular Sequence Data, Animals, Humans, Membrane Proteins, Membranes, Artificial, Phosphorylation, Cells, Cultured, Micelles
Abstract

Laser and neutron scattering experiments showed that in mixed micelles of ganglioside GM2 and GT1b, a membrane mimicking system, the segregation of gangliosides may occur spontaneously. Photolabeling experiments using nitrophenylazide containing ganglioside GM1 proved that gangliosides added to cells in culture enter the cell and bind to its membrane as components of microdomains, which specifically interact with a protein of about 30 kDa. This suggests that ganglioside segregation may be a natural phenomenon. Gangliosides when added to granule cells in culture led to increase in protein phosphorylation, the effect exerted being related to the amount of ganglioside molecules inserted stably into the cell lipid layer and an increase of 0.7% of the cell original ganglioside content promoted an increase of 57% in the incorporation of 32P into cell membrane proteins. From the above results a possible relationship between ganglioside segregation and involvement of ganglioside in enzyme activity control is suggested.

Published
1990

50. Hirudo medicinalis: A new model for testing activators and inhibitors of angiogenesis.

Author

M. de Eguileor, A. Grimaldi, G. Tettamanti, R. Ferrarese, T. Congiu, M. Protasoni, G. Perletti, R. Valvassori, and G. Lanzavecchia

Abstract

An increasing body of evidence indicates that in the leech Hirudo medicinalis the angiogenic process is finely regulated and coordinated by the botryoidal tissue. In this paper we provide evidence on the involvement of botryoidal tissue cells in angiogenesis induced in H. medicinalis by a variety of stimuli including surgical wounds or the administration of modulators of neovascularization. Interestingly, we show that either human activators of vascular cell growth, or anti-angiogenic peptides like angiostatin and endostatin, or the drug mitomycin, can induce a prompt biological response in H. medicinalis. We show as well that angiogenesis in this invertebrate shares a surprising degree of similarity with neovascularization in vertebrates, both at the biochemical and cellular levels, because it involves similar growth factors/growth factor receptors, and relies on analogous cell–cell or cell–matrix interactions. For these reasons we suggest that H. medicinalis can be used as a reproducible model for testing activators or inhibitors of angiogenesis, and for investigating the biochemical, ultrastructural and cellular processes involved in new vessel formation. [ABSTRACT FROM AUTHOR]

Published
2001

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