Go to the content. | Move to the navigation | Go to the site search | Go to the menu | Contacts | Accessibility

| Create Account

Paolo, Pariante (2012) Studio dell'Espressione della Protimosina-Alfa nelle Cellule Germinali Meiotiche e Post-Meiotiche Durante La Prima Ondata Spermatogenetica di Ratto e Negli Spermatozoi Epididimali. [Ph.D. thesis]

Full text disponibile come:

[img]
Preview
PDF Document (Tesi di Dottorato - Paolo Pariante) - Submitted Version
Available under License Creative Commons Attribution No Derivatives.

3722Kb

Abstract (english)

Prothymosin-α (PTMA) is a small, highly acidic protein, first studied in the rat thymus as an immunogenic factor (Haritos et al., 1984a), and soon detected in a wide variety of mammalian tissues, including heart, brain, kidney and gonads (Haritos et al., 1984b; Clinton et al., 1989). The protein is noticeably conserved through evolution: it has been found in all the Mammals studied so far and, only recently, in a restricted number of non-mammalian Vertebrates, such as Rana esculenta, (Aniello et al., 2002), Danio rerio (Donizetti et al., 2008) and Torpedo marmorata (Prisco et al., 2009). PTMA uncommon structural features support the adoption of a native random-coil conformation (Gast et al., 1995), which favours both its interaction with several cationic species and its varied localization, that spans from nuclear and cytoplasmic intracellular environments to the extracellular districts (Enkermann et al., 2000b, Mosoian, 2011), allowing for its established participation in a substantial variety of physiological processes. Among the multiple functions that have been associated with PTMA are cell proliferation, DNA packaging (through its binding to histone H1), activation of transcription, cell survival, and neoplastic transformation, some of which have often been ascribed to molecular mimicry. Only few studies have tried to weigh its possible involvement in reproduction, specifically in male gametogenesis: the first reports suggested that PTMA might be associated with the proliferative and early-meiotic phases of Mammal spermatogenesis (Rosón et al., 1990). Some years later our group started a comparative project on vertebrate spermatogenesis and reported, for the first time, the isolation of the prothymosin in a non-mammalian species, the Amphibian Rana esculenta (Aniello et al., 2002): ptma transcript is highly expressed through the annual reproductive cycle of this frog, peaking in September/October, when meiosis is active and the first phases of spermiogenesis are occurring, and it is localized in I and II spermatocytes (SPC), as well as in the interstitial Leydig cells (LC; Aniello et al., 2002). Consistently, the protein has been found in the germinal compartment, from IISPC to spermatozoa (SPZ), and in the LC (Ferrara et al., 2009). A congruent pattern has been recently highlighted in studies on the fish Torpedo marmorata. Thus, our data have suggested that PTMA could be associated with the meiotic and post-meiotic phases of vertebrate spermatogenesis.
In order to extend our comparison and to evaluate the possible conservation of this pattern in Mammals, in the present work we have studied the correlation between PTMA and the meiotic and post-meiotic phases of rat spermatogenesis. After confirming the presence of both the transcript and its protein in the testes of adult specimens, we focused on the first wave of spermatogenesis, analysing young male gonads sampled at three developmental time points, each one suitable for the thorough observation of specific germ cell (GC) types: 27 dpp (days post-partum), when meiosis has been completed for the first time; 35 dpp, during the spermiogenic phase; 60 dpp, after the end of the first wave, when the testis is fully developed. Our experiments showed that the expression levels of both Ptma mRNA and of the corresponding protein decrease in total extracts from 27 to 60 dpp. The in situ hybridization localized the transcript in interstitial LC, peritubular myoid cells (PMC) and, inside the tubules, in GC from pachytene SPC to the newly formed haploid SPT. The immunohistochemistry analysis localized the protein in the same cell types at 27 dpp, while in the germinal compartment at 35 and 60 dpp PTMA is only detectable in the haploid cells. Further analysis have shown that the protein is associated with the acrosome system throughout its biogenesis, up until its final perinuclear destination in the head of SPZ (Ferrara et al., 2010), as corroborated by immunofluorescence studies on rat and human mature gametes.
Thus, our data reveal, for the first time, that PTMA may play a direct role in the maturation of Mammal SPZ, or even be involved in the subsequent events of fertilization.

Abstract (italian)

La protimosina-α (PTMA) è una proteina acida di piccole dimensioni, studiata per la prima volta nel timo di ratto quale fattore immunogeno (Haritos et al., 1984a), e in seguito identificata in molteplici tessuti dei Mammiferi, tra cui il cervello, il cuore, i reni, e le gonadi (Haritos et al., 1984b; Clinton et al., 1989). La proteina è filogeneticamente conservata: la sua presenza è stata confermata in ogni Mammifero finora studiato, mentre, solo di recente, è stata scoperta in un ristretto numero di Vertebrati non mammiferi, quali Rana esculenta, (Aniello et al., 2002), Danio rerio (Donizetti et al., 2008) e Torpedo marmorata (Prisco et al., 2009). Le atipiche caratteristiche strutturali di PTMA favoriscono l’assunzione di una conformazione nativa random-coil (Gast et al., 1995), che le consente di interagire con numerose molecole di natura cationica. Ciò, insieme alla sua localizzazione, che si estende dal nucleo al citoplasma fino ai distretti extracellulari (Enkermann et al., 2000b, Mosoian, 2011), giustifica la sua partecipazione in una elevata varietà di processi biologici. Tra le innumerevoli funzioni associate a PTMA vi sono la proliferazione cellulare, il rimodellamento della cromatina (tramite il legame all’istone H1), l’attivazione trascrizionale, la difesa dai sistemi di morte cellulare, e la trasformazione neoplastica, ruoli che sono stati spesso spiegati con l’ipotesi del mimetismo molecolare. Pochi studi finora hanno affrontato il possibile coinvolgimento di PTMA nella riproduzione, precisamente nella gametogenesi maschile: i primi riscontri hanno suggerito che la proteina possa essere associata alle fasi proliferative e alle prime fasi meiotiche della spermatogenesi dei Mammiferi (Rosón et al., 1990). In seguito, il nostro gruppo ha dato inizio a un progetto di tipo comparativo sulla spermatogenesi dei vertebrati e ha riportato, per la prima volta, l’isolamento della protimosina in una specie non-mammifera, l’Anfibio Rana esculenta (Aniello et al., 2002): il trascritto di ptma è espresso ad alti livelli durante il ciclo riproduttivo annuale della rana, con un picco in Settembre/Ottobre, quando sono in corso le meiosi e le prime fasi della spermiogenesi, ed è localizzato negli spermatociti
III
(SPC) I e II, e nelle cellule di Leydig (LC; Aniello et al., 2002). Analogamente, la proteina è stata rilevata nel compartimento germinale, dagli SPCII agli spermatozoi (SPZ) e nelle LC (Ferrara et al., 2009). Recentemente, è stato evidenziato un pattern corrispondente nel pesce selaceo Torpedo marmorata. I nostri dati suggeriscono, dunque, che PTMA sia associata alle fasi meiotiche e post-meiotiche della spermatogenesi dei vertebrati.
Allo scopo di proseguire gli studi comparati e di valutare la possibile conservazione del pattern nei mammiferi, nel presente testo abbiamo studiato la correlazione tra PTMA e le fasi meiotiche e post-meiotiche della spermatogenesi di ratto. Per prima cosa abbiamo confermato la presenza del messaggero e della proteina nei testicoli di esemplari adulti, poi ci siamo soffermati sulla prima ondata della spermatogenesi, analizzando gonadi di giovani ratti prelevate a tre tempi di sviluppo, ognuno valido per l’osservazione approfondita di specifiche cellule germinali (CG): 27 giorni dopo la nascita (dpp), momento in cui le meiosi sono state completate per la prima volta; 35 dpp, durante la spermiogenesi; 60 al termine della prima ondata, quando il testicolo è ormai maturo. I nostri dati mostrano che sia i livelli di espressione dell’mRNA di Ptma, sia della proteina subiscono una riduzione da 27 a 60 dpp. L’ibridazione in situ ha permesso di localizzare il trascritto nelle LC e nelle cellule peritubulari mioidi (PMC) e, nei tubuli, dagli SPC in pachitene agli SPT aploidi di nuova formazione. L’analisi di immunoistochimica ha mostrato che la proteina si trova negli stessi tipi cellulari a 27 dpp, mentre nel compartimento germinale a 35 e a 60 dpp è rilevabile solo nelle cellule aploidi (Ferrara et al., 2010). Ulteriori indagini hanno mostrato che PTMA è associata al sistema acrosomale durante tutto il processo di biogenesi, fino alla sua destinazione perinucleare nella testa dello SPZ, come supportato da studi di immunofluorescenza su gameti maturi di ratto e uomo.
Pertanto, i nostri dati rivelano, per la prima volta, che PTMA potrebbe avere un ruolo diretto nella maturazione degli SPZ dei Mammiferi, o addirittura concorrere alla realizzazione degli eventi successivi della fecondazione.

Statistiche Download - Aggiungi a RefWorks
EPrint type:Ph.D. thesis
Tutor:Minucci, Sergio
Ph.D. course:Ciclo 24 > Scuole 24 > BIOLOGIA E MEDICINA DELLA RIGENERAZIONE > ENDOCRINOLOGIA COMPARATA
Data di deposito della tesi:20 January 2012
Anno di Pubblicazione:20 January 2012
Key Words:Prot-alpha, Prot-alfa, PTMA, prothymosin-alpha, protimosina-alfa, spermatogenesis, spermatogenesi, spermatozoa, spermatozoi, SPZ, rat, ratto, Rattus norvegicus, Testis, testicoli
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/11 Biologia molecolare
Struttura di riferimento:Dipartimenti > pre 2012 - Dipartimento di Scienze Farmaceutiche
Codice ID:4410
Depositato il:19 Nov 2012 11:36
Simple Metadata
Full Metadata
EndNote Format

Bibliografia

I riferimenti della bibliografia possono essere cercati con Cerca la citazione di AIRE, copiando il titolo dell'articolo (o del libro) e la rivista (se presente) nei campi appositi di "Cerca la Citazione di AIRE".
Le url contenute in alcuni riferimenti sono raggiungibili cliccando sul link alla fine della citazione (Vai!) e tramite Google (Ricerca con Google). Il risultato dipende dalla formattazione della citazione.

Adams MD, Kerlavage AR, Fleischmann RD, Fuldner RA, Bult CJ, Lee NH, Kirkness EF, Weinstock KG, Gocayne JD, White O, et al. 1995. Initial assessment of human gene diversity and expression patterns based upon 83 million nucleotides of cDNA sequence.377:3-174 Cerca con Google

Aniello F, Branno M, De Rienzo G, Ferrara D, Palmiero C, Minucci S. 2002. First evidence of prothymosin alpha in a non-mammalian vertebrate and its involvement in the spermatogenesis of the frog Rana esculenta. Mech Dev. 110:213-7 Cerca con Google

Barbini L, Gonzalez R, Dominguez F, Vega F. 2006. Apoptotic and proliferating hepatocytes differ in prothymosin alpha expression and cell localization. Mol Cell Biochem. 291:83-91 Cerca con Google

Barcia MG, Castro JM, Jullien CD, Freire M. 1993. Prothymosin alpha is phosphorylated in proliferating stimulated cells. J Biol Chem. 268:4704-8 Cerca con Google

Baxevanis CN, Reclos GJ, Panneerselvam C, Papamichail M. 1988. Enhancement of human T lymphocyte functions by prothymosin alpha. I. Augmentation of mixed lymphocyte culture reactions and soluble protein-induced proliferative responses. Immunopharmacology. 15:73-84 Cerca con Google

Baxevanis CN, Thanos D, Reclos GJ, Anastasopoulos E, Tsokos GC, Papamatheakis J, Papamichail M. 1992. Prothymosin alpha enhances human and murine MHC class II surface antigen expression and messenger RNA accumulation. J Immunol. 148:1979-84 Cerca con Google

Bellvé AR. 1988. Purification and characterization of mouse protamines P1 and p2. Amino acid sequence of P2. Biochemistry 27:2890-97 Cerca con Google

Bianco NR, Montano MM. 2002. Regulation of prothymosin alpha by estrogen receptor alpha: molecular mechanisms and relevance in estrogen-mediated breast cell growth. Oncogene 2002. 21:5233-44. Erratum in Oncogene 2002. 21:8221 Cerca con Google

Boán F, Viñas A, Buceta M, Domínguez F, Sánchez L, Gómez-Márquez J. 2001. Prothymosin alpha, a mammalian c-myc-regulated acidic nuclear protein, provokes the decondensation of human chromosomes in vitro. 93:171-4 Cerca con Google

Brewer L, Corzett M, Balhorn R. 2002. Condensation of DNA by spermatid basic nuclear proteins. J Biol Chem 277:38895-900 Cerca con Google

Caldarella J, Goodall GJ, Felix AM, Heimer EP, Salvin SB, Horecker BL. 1983. Thymosin alpha 11: a peptide related to thymosin alpha 1 isolated from calf thymosin fraction 5. Proc Natl Acad Sci USA. 80:7424-7 Cerca con Google

Clermont Y, Perey B. 1957. Quantitative study of the cell population of the seminiferous tubules in immature rats. AM J Anat. 100:241-267 Cerca con Google

Clermont Y, Tang XM. 1985. Glycoprotein synthesis in the Golgi apparatus of spermatids during spermiogenesis of the rat. Anat Rec213:33-43. Cerca con Google

Clermont Y. 1966. Renewal of spermatogonia in man. Am J Anat. 118:509-24 Cerca con Google

Clinton M, Frangou-Lazaridis M, Panneerselvam C, Horecker BL. 1989. Prothymosin alpha and parathymosin: mRNA and polypeptide levels in rodent tissues. Arch Biochem Biophys. 269:256-63 Cerca con Google

Cotter MA 2nd, Robertson ES. 2000. Modulation of histone acetyltransferase activity through interaction of epstein-barr nuclear antigen 3C with prothymosin alpha. Mol Cell Biol. 20:5722-35 Cerca con Google

Davidoff MS, Breucker H, Holstein AF, Seidi K. 1990. Cellular architecture of the lamina propria of human seminiferous tubules. Cell Tissue Res. 262:254-61 Cerca con Google

Davidoff MS, Shulze W, Middendorff R, Holstein AF. 1993. The Leydig cell of the human testis – a new member of the diffuse neuroendocrine system. Cell Tissue Res 271:429-39. Cerca con Google

De Rienzo G, Di Sena R, Ferrara D, Palmiero C, Chieffi Baccari G, Minucci S. 2002. Temporal and spatial localization of prothymosin alpha transcript in the Harderian gland of the frog, Rana esculenta. J Exp Zool. 292:633-9 Cerca con Google

Deurdulian C, Mittelstaedt CA, Chong WK, Fielding JR. 2007. US of acute scrotal trauma: optimal technique, imaging findings, and management. Radiographics 27:357-69 Cerca con Google

Díaz-Jullien C, Pérez-Estévez A, Covelo G, Freire M. 1996. Prothymosin alpha binds histones in vitro and shows activity in nucleosome assembly assay. Biochim Biophys Acta. 1296:219-27 Cerca con Google

Dominguez F, Magdalena C, Cancio E, Roson E, Paredes J, Loidi L, Zalvide J, Fraga M, Forteza J, Regueiro BJ, et al. 1993. Tissue concentrations of prothymosin alpha: a novel proliferation index of primary breast cancer. Eur J Cancer. 29A:893-7 Cerca con Google

Donizetti A, Liccardo D, Esposito D, Del Gaudio R, Locascio A, Ferrara D, Minucci S, Aniello F. 2008. Differential expression of duplicated genes for prothymosin alpha during zebrafish development. Dev Dyn. 237:1112-8 Cerca con Google

Dosil M, Freire M, Gómez-Márquez J. 1990. Tissue-specific and differential expression of prothymosin alpha gene during rat development. FEBS Lett. 269:373-6 Cerca con Google

Dym M, Fawcett DW. 1971. Further ovservations on the numbers of spermatogonia, spermatocytes, and spermatids connected by intercellular bridges in the mammalian testis. Biol Reprod. 4:195-215 Cerca con Google

Earnshaw WC. 1987. Anionic regions in nuclear proteins. J Cell Biol. 105:1479-82 Cerca con Google

Eddy E, O’Brien DA. 1994. The spermatozoon. In: Knobil E, Neill JD, editors. The physiology of reproduction. New York: Raven Press. 29-77 Cerca con Google

Enkemann SA, Wang RH, Trumbore MW, Berger SL. 2000a. Functional discontinuities in prothymosin alpha caused by caspase cleavage in apoptotic cells. J Cell Physiol. 182:256-68 Cerca con Google

Enkemann SA, Ward RD, Berger SL. 2000b. Mobility within the nucleus and neighboring cytosol is a key feature of prothymosin-alpha. 48:1341-55 Cerca con Google

Eschenfeldt WH, Manrow RE, Krug MS, Berger SL. 1989. Isolation and partial sequencing of the human prothymosin alpha gene family. Evidence against export of the gene products. J Biol Chem. 264:7546-55 Cerca con Google

Evstaf'eva AG, Karapetian RN, Rubtsov IuP, Filonov GS, Abaeva IS, Fateeva TV, Mel'nikov SV, Chichkova NV, Vartapetian AB. 2005 [Novel functions of the well-known protein--prothymosin alpha is involved in protection of cells against apoptosis and oxidative stress]. [Article in Russian]. Mol Biol (Mosk). 39:729-45 Cerca con Google

Evstafieva AG, Belov GA, Rubtsov YP, Kalkum M, Joseph B, Chichkova NV, Sukhacheva EA, Bogdanov AA, Pettersson RF, Agol VI, Vartapetian AB. 2003. Apoptosis-related fragmentation, translocation, and properties of human prothymosin alpha. Exp Cell Res. 284:211-23 Cerca con Google

Ferrara D, Izzo G, Liguori L, d'Istria M, Aniello F, Minucci S. 2009. Evidence for the involvement of prothymosin alpha in the spermatogenesis of the frog Rana esculenta. J Exp Zool A Ecol Genet Physiol. 311: 1-10 Cerca con Google

Ferrara D, Izzo G, Pariante P, Donizetti A, d'Istria M, Aniello F, Minucci S. 2010. Expression of prothymosin alpha in meiotic and post-meiotic germ cells during the first wave of rat spermatogenesis. J Cell Physiol. 224:362-8 Cerca con Google

Fouquet JP, Kann ML. 1994. The cytoskeleton of mammalian spermatozoa. Biol Cell. 81:89-93 Cerca con Google

Frangou-Lazaridis M, Clinton M, Goodall GJ, Horecker BL. 1988. Prothymosin alpha and parathymosin: amino acid sequences deduced from the cloned rat spleen cDNAs. Arch Biochem Biophys. 263:305-10 Cerca con Google

Garbin F, Eckert K, Immenschuh P, Kreuser ED, Maurer HR. 1997. Prothymosin alpha 1 effects, in vitro, on the antitumor activity and cytokine production of blood monocytes from colorectal tumor patients. Int J Immunopharmacol. 19:323-32 Cerca con Google

Gast K, Damaschun H, Eckert K, Schulze-Forster K, Maurer HR, Müller-Frohne M, Zirwer D, Czarnecki J, Damaschun G. 1995. Prothymosin alpha: a biologically active protein with random coil conformation. Biochemistry. 34:13211-8 Cerca con Google

Gaubatz S, Meichle A, Eilers M. 1994. An E-box element localized in the first intron mediates regulation of the prothymosin alpha gene by c-myc. Mol Cell Biol. 14:3853-62 Cerca con Google

George EM, Brown DT. 2010. Prothymosin alpha is a component of a linker histone chaperone. FEBS Lett. 584:2833-6 Cerca con Google

Golan R, Cooper TG, Oschry Y, Oberpenning F, Schulze H, Shochat L, Lewin LM. 1996. Changes in chromatin condensation of human spermatozoa during epididymal transit as determined by flow cytometry. Hum Reprod 11:1457-62 Cerca con Google

Goldstein A, White A. 1970. The thymus as endocrine gland. In: G Litwack editors. Biochemical Actions of Hormones. New York: Academic Press Cerca con Google

Goldstein AL, Guha A, Zatz MM, Hardy MA, White A. 1972. Purification and biological activity of thymosin, a hormone of the thymus gland. Proc Natl Acad Sci USA. 69:1800-3 Cerca con Google

Goldstein AL, Low TL, McAdoo M, McClure J, Thurman GB, Rossio J, Lai CY, Chang D, Wang SS, Harvey C, Ramel AH, Meienhofer J. 1977. Thymosin alpha1: isolation and sequence analysis of an immunologically active thymic polypeptide. Proc Natl Acad Sci USA. 74:725-9. Cerca con Google

Goldstein AL, Stater FD, White A. 1966. Preparation, assay, and partial purification of a thymic lymphocytopoietic factor (thymosin). Proc Nat Acad Sci USA. 56:1010-17 Cerca con Google

Goldstein AL, Thurman GB, Cohen GH, Hooper JA. 1975. Thymosin chemistry, biology and clinical applications. In: Van Bekkum DW editors. Biological Activity of Thymic Hormones. Rotterdam: Kooyker Scientific Pub. pp 173-197 Cerca con Google

Gómez-Márquez J, Rodríguez P. 1998. Prothymosin alpha is a chromatin-remodelling protein in mammalian cells. Biochem J. 333:1-3 Cerca con Google

Gómez-Márquez J. 2007. Function of prothymosin alpha in chromatin decondensation and expression of thymosin beta-4 linked to angiogenesis and synaptic plasticity. Ann N Y Acad Sci. 1112:201-9 Cerca con Google

Goodall GJ, Dominguez F, Horecker BL. 1986. Molecular cloning of cDNA for human prothymosin alpha. Proc Natl Acad Sci USA. 83:8926-8 Cerca con Google

Gregoire C, Duchateau G. 1956. A study on lympho-epithelial symbiosis in thymus; reactions on the lymphatic tissue to extracts and to implants of epithelial components of thymus. Arch Biol (Liege). 67:269-96 Cerca con Google

Guan J. 2009. Mammalian sperm flagella and cilia. Published by Karolinska Institutet. Cerca con Google

Hannappel E, Huff T. 2003. The thymosins. Prothymosin alpha, parathymosin, and beta-thymosins: structure and function. Vitam Horm. 66:257-96 Cerca con Google

Haritos AA, Goodall GJ, Horecker BL. 1984a. Prothymosin alpha: isolation and properties of the major immunoreactive form of thymosin alpha 1 in rat thymus. Proc Natl Acad Sci USA. 81:1008-11 Cerca con Google

Haritos AA, Tsolas O, Horecker BL. 1984b. Distribution of prothymosin alpha in rat tissues. Proc Natl Acad Sci USA. 81:1391-3 Cerca con Google

Hess RA. 1998. Spermatogenesis, overview. In: Knobil E, Neill JD, editors. Encyclopedia of Reproduction vol.4, San Diego: Academic Press. pp 539-545 Cerca con Google

Holstein AF, Maekawa M, Nagano T, Davidoff MS. 1996. Myofibroblasts in the lamina propria of human seminiferous tubules are dynamic structures of heterogenous phenotype. Arch Histol Cytol. 59:109-125 Cerca con Google

Hooper JA, McDaniel MC, Thurman GB, Cohen GH, Schulof RS, Goldstein AL. 1975. Purification and properties of bovine thymosin. Ann N Y Acad Sci. 249:125-44 Cerca con Google

Hud NV, Allen Mj, Downing KH, Lee J, Balhorn R. 1993. Identification of the elemental packing unit of DNA in mammalian sperm cells by atomic force microscopy. Biochem Biophys Res Commun 193:1347-54 Cerca con Google

Jiang X, Kim HE, Shu H, Zhao Y, Zhang H, Kofron J, Donnelly J, Burns D, Ng SC, Rosenberg S, Wang X. 2003. Distinctive roles of PHAP proteins and prothymosin-alpha in a death regulatory pathway. Science. 299:223-6 Cerca con Google

Johnson GD, Lalancette C, Linnermann AK, Leduc F, Boissonneault G, Krawetz SA. 2011. The sperm nucleus: chromatin, RNA, and the nuclear matrix. 141:21-36 Cerca con Google

Karetsou Z, Kretsovali A, Murphy C, Tsolas O, Papamarcaki T. 2002. Prothymosin alpha interacts with the CREB-binding protein and potentiates transcription. EMBO Rep. 3:361-6 Cerca con Google

Karetsou Z, Martic G, Tavoulari S, Christoforidis S, Wilm M, Gruss C, Papamarcaki T. 2004. Prothymosin alpha associates with the oncoprotein SET and is involved in chromatin decondensation. FEBS Lett. 577:496-500 Cerca con Google

Karetsou Z, Sandaltzopoulos R, Frangou-Lazaridis M, Lai CY, Tsolas O, Becker PB, Papamarcaki T. 1998. Prothymosin alpha modulates the interaction of histone H1 with chromatin. Nucleic Acids Res. 26:3111-8 Cerca con Google

Kelly K, Siebenlist U. 1986. The regulation and expression of c-myc in normal and malignant cells. Annu Rev Immunol. 4:317-38 Cerca con Google

Kierszenbaum AL, Tres LL. 1975. Structural and transcriptional features of the mouse spermatid genome. J Cell Biol. 65:258-70 Cerca con Google

Kim KS, Cha MC, Gerton GL. 2001a. Mouse sperm protein sp56 is a component of the acrosomal matrix. Biol Reprod 64:36-43 Cerca con Google

Kim KS, Foster JA, Gerton GL. 2001b. Differential release of guinea pig sperm acrosomal components during exocytosis. Biol Reprod 64:148-156 Cerca con Google

Kimmins S, Sassone-Corsi P. 2005. Chromatin remodeling and epigenetic features of germ cells. Nature 434:583-589 Cerca con Google

Klein JJ, Goldstein AL, White A. 1966. Effects of the thymus lymphocytopoietic factor. Ann N Y Acad Sci. 135:485-95. Cerca con Google

Knight JS, Lan K, Subramanian C, Robertson ES. 2003. Epstein-Barr virus nuclear antigen 3C recruits histone deacetylase activity and associates with the corepressors mSin3A and NCoR in human B-cell lines. J Virol. 77:4261-72 Cerca con Google

Kobayashi T, Wang T, Maezawa M, Kobayashi M, Ohnishi S, Hatanaka K, Hige S, Shimizu Y, Kato M, Asaka M, Tanaka J, Imamura M, Hasegawa K, Tanaka Y, Brachmann RK. 2006. Overexpression of the oncoprotein prothymosin alpha triggers a p53 response that involves p53 acetylation. Cancer Res. 66:3137-44 Cerca con Google

Kuretake S, Kimura Y, Hoshi K, Yanagimachi R. 1996. Fertilization and development of mouse oocytes injected with isolated sperm heads. Biol Reprod 55:789-95 Cerca con Google

Kurtz K, Martinez-Soler F, Ausio J, Chiva M. 2007. Acetylation of histone H4 in complex structural transitions of spermiogenic chromatin. J Cell Biochem 102:1432-41 Cerca con Google

Letsas KP, Frangou-Lazaridis M, Skyrlas A, Tsatsoulis A, Malamou-Mitsi V. 2005. Transcription factor-mediated proliferation and apoptosis in benign and malignant thyroid lesions. Pathol Int. 55:694-702 Cerca con Google

Low TL, Goldstein AL. 1985. Thymosin alpha 1 and polypeptide beta 1. Methods Enzymol. 116:233-48 Cerca con Google

Magdalena C, Dominguez F, Loidi L, Puente JL. 2000. Tumour prothymosin alpha content, a potential prognostic marker for primary breast cancer. Br J Cancer 82:584-90 Cerca con Google

Malicet C, Giroux V, Vasseur S, Dagorn JC, Neira JL, Iovanna JL. 2006. Regulation of apoptosis by the p8/prothymosin alpha complex. Proc Natl Acad Sci USA. 103:2671-6 Cerca con Google

Malo AF, Gomendio M, Garde J, Lang-Lenton B, Soler AJ, Roldan ER. 2006. Sperm design and sperm function. Biol Lett. 2:246-9 Cerca con Google

Manrow RE, Berger SL. 1993. GAG triplets as splice acceptors of last resort. An unusual form of alternative splicing in prothymosin alpha pre-mRNA. J Mol Biol. 234:281-8 Cerca con Google

Manrow RE, Leone A, Krug MS, Eschenfeldt WH, Berger SL. 1992. The human prothymosin alpha gene family contains several processed pseudogenes lacking deleterious lesions. Genomics 13:319-31. Cerca con Google

Martini PG, Delage-Mourroux R, Kraichely DM, Katzenellenbogen BS. 2000. Prothymosin alpha selectively enhances estrogen receptor transcriptional activity by interacting with a repressor of estrogen receptor activity. Mol Cell Biol. 20:6224-32 Cerca con Google

Martini PG, Katzenellenbogen BS. 2003. Modulation of estrogen receptor activity by selective coregulators. J Steroid Biochem Mol Biol. 85:117-22 Cerca con Google

Middendorff R, Muller D, Mewe M, Mukhopadhyay AK, Holstein AF, Davidoff MS. 2002. The tunica albuginea of the human testis is characterized by complex contraction and relaxation activities regulated by cyclic GMP. J Clin Endocrinol Metabol 87:3486-99 Cerca con Google

Monesi V, Geremia R, D'Agostino A, Boitani C. 1978. Biochemistry of male germ cell differentiation in mammals: RNA synthesis in meiotic and postmeiotic cells. Curr Top Dev Biol. 12:11-36 Cerca con Google

Moody TW, Leyton J, Zia F, Tuthill C, Badamchian M, Goldstein AL. 2000. Thymosinalpha1 is chemopreventive for lung adenoma formation in A/J mice. Cancer Lett 155: 121-7 Cerca con Google

Mori M, Barnard GF, Staniunas RJ, Jessup JM, Steele GD Jr, Chen LB. 1993. Prothymosin-alpha mRNA expression correlates with that of c-myc in human colon cancer. Oncogene. 8:2821-6 Cerca con Google

Mosoian A, Teixeira A, Burns CS, Khitrov G, Zhang W, Gusella L, Klotman P, Klotman M. 2007. Influence of prothymosin-alpha on HIV-1 target cells. Ann N Y Acad Sci. 1112:269-85 Cerca con Google

Mosoian A, Teixeira A, High AA, Christian RE, Hunt DF, Shabanowitz J, Liu X, Klotman M. 2006. Novel function of prothymosin alpha as a potent inhibitor of human immunodeficiency virus type 1 gene expression in primary macrophages. J Virol. 80:9200-6 Cerca con Google

Mosoian A. 2011. Intracellular and extracellular cytokine-like functions of prothymosin α: implications for the development of immunotherapies. Future Med Chem. 3:1199-208. Cerca con Google

Oko R, Clermont Y. 1998. Spermiogenesis. In: Knobil, E., Neill, J.D. editors. Encyclopedia of Reproduction. San Diego: Academic Press. pp 602-609. Cerca con Google

Oko R, Maravei D. 1994. Protein composition of the perinuclear theca of bull spermatozoa. Biol Reprod 50:1000-1014. Cerca con Google

Oko R, Sutovsky P. 2009. Biogenesis of sperm perinuclear theca and its role in sperm functional competence and fertilization. J Reprod Immunol 83:2-7 Cerca con Google

Oko R. 1995. Developmental expression and possible role of perinuclear theca proteins in mammalian spermatozoa. Reprod Fertil Dev 7:777-797 Cerca con Google

Orre RS, Cotter MA 2nd, Subramanian C, Robertson ES. 2001. Prothymosin alpha functions as a cellular oncoprotein by inducing transformation of rodent fibroblasts in vitro. J Biol Chem. 276:1794-9 Cerca con Google

Pan LX, Haritos AA, Wideman J, Komiyama T, Chang M, Stein S, Salvin SB, Horecker BL. 1986. Human prothymosin alpha: amino acid sequence and immunologic properties. Arch Biochem Biophys. 250:197-201 Cerca con Google

Papamarcaki T, Tsolas O. 1994. Prothymosin alpha binds to histone H1 in vitro. FEBS Lett. 345:71-5 Cerca con Google

Pereira-Leal JB, Seabra M.C. 2001. Evolution of the Rab family of small GTP-binding proteins. J Mol Biol 313:889-901. Cerca con Google

Piñeiro A, Cordero OJ, Nogueira M. 2000. Fifteen years of prothymosin alpha: contradictory past and new horizons. Peptides. 21:1433-46 Cerca con Google

Pivot-Pajot C, Caron C, Govin K, Vion A, Rousseaux S, Khochbin S. 2003. Acetylation-dependent chromatin reorganization by BRDT, a testis-specific bromodomain-containing protein. Moll Cell Biol 23:5354-65 Cerca con Google

Prisco M, Donizetti A, Aniello F, Locascio A, Del Giudice G, Agnese M, Angelini F, Andreuccetti P. 2009. Expression of Prothymosin alpha during the spermatogenesis of the spotted ray Torpedo marmorata. Gen Comp Endocrinol. 164:70-6 Cerca con Google

Qiu L, Guo BY, Miao H, Dao SY, Zhang R, Yuan PQ, Yang X. 2002. [Effect of recombinant prothymosin alpha on secretion of IFN-gamma, IFN-alpha and TNF-alpha in vitro]. [Article in Chinese]. Yao Xue Xue Bao. 37:326-8 Cerca con Google

Rathke C, Barkmann B, Burkhard S, Jayaramaiah-Raja S, Roote J, Renkawitz-Pohl R. 2010. Distinct functions of Mst77F and protamines in nuclear shaping and chromatin condensation during Drosophila spermiogenesis. Eur J Cell Biol 89:326-38 Cerca con Google

Reclos GJ, Baxevanis CN, Sfagos C, Papageorgiou C, Tsokos GC, Papamichail M. Multiple sclerosis: II. Effects of prothymosin alpha on the autologous and allogeneic MLR in patients with multiple sclerosis. Clin Exp Immunol. 70:336-44 Cerca con Google

Roberts S, White A. 1949. Biochemical characterization of lymphoid tissue proteins. J Biol Chem. 178:151-62 Cerca con Google

Rodríguez P, Viñuela JE, Alvarez-Fernández L, Buceta M, Vidal A, Domínguez F, Gómez-Márquez J. 1998. Overexpression of prothymosin alpha accelerates proliferation and retards differentiation in HL-60 cells. Biochem J. 331:753-61 Cerca con Google

Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, Pitzurra L, Bellocchio S, Velardi A, Rasi G, Di Francesco P, Garaci E. 2004. Thymosin alpha 1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 103:4232-9 Cerca con Google

Rosón E, Gallego R, García-Caballero T, Heimer EP, Felix AM, Domínguez F. 1990. Prothymosin alpha expression is associated to cell division in rat testis. Histochemistry. 94:597-9 Cerca con Google

Rousseaux S, Ferro M. 2009. Epigenetics of spermiogenesis combining in silico and proteomic approaches in the mouse model. In Bioinformatics for system biology 2nd ed., SA Krawetz editors. New York: Humana Press. pp 106-117 Cerca con Google

Rubtsov IuP, Vartapetian AB. 1995. [New intronless members of human prothymosin alpha genes]. [Article in Russian]. Mol Biol (Mosk). 29:1320-5 Cerca con Google

Russell LD, Griswold MD. 1993. The Sertoli Cell. Cache River Press, Clearwater FL. Mol Reprod Dev 36:517 Cerca con Google

Sarandeses CS, Covelo G, D Díaz-Jullien C, Freire M. 2003. Prothymosin alpha is processed to thymosin alpha 1 and thymosin alpha 11 by a lysosomal asparaginyl endopeptidase. J Biol Chem. 278:13286-93 Cerca con Google

Sburlati AR, De La Rosa A, Batey DW, Kurys GL, Manrow RE, Pannell LK, Martin BM, Sheeley DM, Berger SL. 1993. Phosphorylation of human and bovine prothymosin alpha in vivo. Biochemistry. 32:4587-96 Cerca con Google

Sburlati AR, Manrow RE, Berger SL. 1991. Prothymosin alpha antisense oligomers inhibit myeloma cell division. Proc Natl Acad Sci USA. 88:253-7. Cerca con Google

Schulof RS, Goldstein AL. 1981. In: Hadden JW, Stewart WR editors. The Lymphokines, Biochemistrey and Biological Activity. Clinton, NJ: Humana Press. pp 397-423 Cerca con Google

Skopeliti M, Iconomidou VA, Derhovanessian E, Pawelec G, Voelter W, Kalbacher H, Hamodrakas SJ, Tsitsilonis OE. 2009. Prothymosin alpha immunoactive carboxyl-terminal peptide TKKQKTDEDD stimulates lymphocyte reactions, induces dendritic cell maturation and adopts a beta-sheet conformation in a sequence-specific manner. Mol Immunol. 46:784-92 Cerca con Google

Skopeliti M, Voutsas IF, Klimentzou P, Tsiatas ML, Beck A, Bamias A, Moraki M, Livaniou E, Neagu M, Voelter W, Tsitsilonis OE. 2006a. The immunologically active site of prothymosin alpha is located at the carboxy-terminus of the polypeptide. Evaluation of its in vitro effects in cancer patients. Cancer Immunol Immunother. 55:1247-57 Cerca con Google

Subramanian C, Hasan S, Rowe M, Hottiger M, Orre R, Robertson ES. 2002. Epstein-Barr virus nuclear antigen 3C and prothymosin alpha interact with the p300 transcriptional coactivator at the CH1 and CH3/HAT domains and cooperate in regulation of transcription and histone acetylation. J Virol. 76:4699-708 Cerca con Google

Suzuki S, Takahashi S, Takahashi S, Takeshita K, Hikosaka A, Wakita T, Nishiyama N, Fujita T, Okamura T, Shirai T. 2006. Expression of prothymosin alpha is correlated with development and progression in human prostate cancers. Prostate. 66:463-9 Cerca con Google

Szabo P, Panneerselvam C, Clinton M, Frangou-Lazaridis M, Weksler D, Whittington E, Macera MJ, Grzeschik KH, Selvakumar A, Horecker BL. 1993. Prothymosin alpha gene in humans: organization of its promoter region and localization to chromosome 2. Human Genet. 90:629-34 Cerca con Google

Tang XM, Lalli MF Clermont Y. 1982. A cytochemical study of the Golgi apparatus of the spermatid during spermiogenesis in the rat. Am J Anat 163: 283-294 Cerca con Google

Thorne-Tjomsland G, Clermont Y, Hermo L. 1988. Contribution of the Golgi apparatus components to the formation of the acrosomic system and chromatoid body in rat spermatids. Anat Rec 221:591-598 Cerca con Google

Thurman A, Ahmed A, Strong M, Gershwin ME, Steinberg AD, Goldstein AL. 1975. Thymosin induced increase in mitogenic responsiveness of C57BL/6J, NZB/W, and nude mice. Trans Proc 7:299-303 Cerca con Google

Trumbore MW, Manrow RE, Berger SL. 1998. Prothymosin alpha is not found in yeast. Protein Expr Purif. 1998 13:383-8 Cerca con Google

Trumbore MW, Wang RH, Enkemann SA, Berger SL. 1997. Prothymosin alpha in vivo contains phosphorylated glutamic acid residues.J Biol Chem. 272:26394-404 Cerca con Google

Tsai YS, Jou YC, Lee GF, Chen YC, Shiau AL, Tsai HT, Wu CL, Tzai TS. 2009. Aberrant prothymosin-alpha expression in human bladder cancer. Urology. 73:188-92 Cerca con Google

Tsitsiloni OE, Stiakakis J, Koutselinis A, Gogas J, Markopoulos C, Yialouris P, Bekris S, Panoussopoulos D, Kiortsis V, Voelter W, et al. 1993. Expression of alpha-thymosins in human tissues in normal and abnormal growth. Proc Natl Acad Sci USA. 90:9504-7 Cerca con Google

Ueda H, Matsunaga H, Uchida H, Ueda M. 2010. Prothymosin alpha as robustness molecule against ischemic stress to brain and retina. Ann Ny Acad Sci. 1194:20-6 Cerca con Google

Ueda H. 2008. Prothymosin alpha plays a key role in cell death mode-switch, a new concept for neuroprotective mechanisms in stroke. Naunyn Schmiedebergs Arch Pharmacol. 377:315-23. Cerca con Google

Ueda H. 2009. Prothymosin alpha and cell death mode switch, a novel target for the prevention of cerebral ischemia-induced damage. Pharmacol Ther. 123:32333 Cerca con Google

Vareli K, Tsolas O, Frangou-Lazaridis M. 1996. Regulation of prothymosin alpha during the cell cycle. Eur J Biochem 238:799-806 Cerca con Google

Voutsas IF, Baxevanis CN, Gritzapis AD, Missitzis I, Stathopoulos GP, Archodakis G, Banis C, Voelter W, Papamichail M. 2000. Synergy between interleukin-2 and prothymosin alpha for the increased generation of cytotoxic T lymphocytes against autologous human carcinomas. Cancer Immunol Immunother. 49:449-58 Cerca con Google

Wang C, Fu M, Angeletti RH, Siconolfi-Baez L, Reutens AT, Albanese C, Lisanti MP, Katzenellenbogen BS, Kato S, Hopp T, Fuqua SA, Lopez GN, Kushner PJ, Pestell RG. 2001. Direct acetylation of the estrogen receptor alpha hinge region by p300 regulates transactivation and hormone sensitivity. J Biol Chem. 276:18375-83 Cerca con Google

Wang M, Pan JY. 2007. Prothymosin alpha and tumor: current status and perspective. Chin J Cancer. 26:333-336 Cerca con Google

Wassarman PM. 1999. Mammalian fertilization: molecular aspects of gamete adhesion, exocytosis, and fusion. Cell 96:175-183 Cerca con Google

Wu CG, Boers W, Reitsma PR, van Deventer SJ, Chamuleau RA. 1997. Overexpression of prothymosin alpha, concomitant with c-myc, during rat hepatic carcinogenesis. Biochem Biophys Res Commun. 232:817-21 Cerca con Google

Wu CG, Habib NA, Mitry RR, Reitsma PH, van Deventer SJ, Chamuleau RA. 1997. Overexpression of hepatic prothymosin alpha, a novel marker for human hepatocellular carcinoma. Br J Cancer. 76:1199-204 Cerca con Google

Wykes SM, Krawetz SA. 2003. The structural organization of sperm chromatin. J Biol Chem. 278:29471-7 Cerca con Google

Yanagimachi R. 1994. Mammalian fertilization. In: Knobil E, Neill JD, editors. The physiology of reproduction. New York: Raven Press. pp 189-317 Cerca con Google

Yoshinaga K, Toshimori K. 2003. Organization and modifications of sperm acrosomal molecules during spermatogenesis and epidydimal maturation. Microsc Res Tech. 61:39-45 Cerca con Google

Zhao R, Gish K, Murphy M, Yin Y, Notterman D, Hoffman WH, Tom E, Mack DH, Levine AJ. 2000. Analysis of p53-regulated gene expression patterns using oligonucleotide arrays. 14:981-93 Cerca con Google

Zlatanova J, van Holde K. 1996. The linker histones and chromatin structure: new twists. Prog Nucleic Acid Res Mol Biol. 52:217-59 Cerca con Google

Download statistics

Solo per lo Staff dell Archivio: Modifica questo record