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E Grassilli

Publications and source records attributed to E Grassilli.

31 records · Page 2Linked to original sources
PubMed1993

Transcription factors DNA-binding activity in rat thymocytes undergoing apoptosis after heat-shock or dexamethasone treatment.

The onset of apoptosis is generally thought to require the induction of a novel genetic program. Accordingly, we studied the kinetic of DNA-binding activity of several transcription factors in rat thymocytes undergoing apoptosis induced by dexamethasone (DEX) or heat shock (HS) treatment. Here we report that: 1) early activation of AP-1 occurred in both models of apoptosis, even if the intensity of activation and AP-1 complex composition were different and much less evident in HS-treated thymocytes; 2) early NFkB DNA-binding activity was also observed in both types of apoptosis; 3) downregulation of other transcription factors, such as OCT-1 and CREB, with high constitutive activity, was recorded in both models of apoptosis. The fact that some TFs are up-regulated while others are down-regulated suggests that apoptosis is the result of a complex combination of positive and negative signals regulating gene expression.

Animals↗
PubMed1993

Studies of the relationship between cell proliferation and cell death. III. AP-1 DNA-binding activity during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes.

In previous papers we started to investigate the possible relationship existing between cell proliferation and cell death. We reported that in rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment, an induction of c-fos and c-jun occurs with different but partially overlapping kinetics (Grassilli et al., BBRC, 1992, 188, 1261-1266). To test the hypothesis that, in both processes, the early induction of these nuclear oncogenes is necessary to allow the induction of later-expressed genes regulated at the transcriptional level by AP-1 complex, AP-1 DNA-binding activity was investigated in the aforementioned model. Indeed, we found that AP-1 is activated not only in proliferating but also in apoptotic cells, with a kinetics in accord with our data about c-fos and c-jun mRNA accumulation in the same experimental model. Moreover, our findings suggest that an interaction between AP-1 and glucocorticoid receptor also occurs in our model of dexamethasone-mediated apoptosis.

Animals↗
PubMed1992

Studies of the relationship between cell proliferation and cell death. II. Early gene expression during concanavalin A-induced proliferation or dexamethasone-induced apoptosis of rat thymocytes.

Several data in the literature suggest that an intriguing relationship exists between cell proliferation and cell death. Accordingly, we studied the early expression of different genes in the same cells, i.e. rat thymocytes, undergoing cell proliferation upon stimulation with Concanavalin A or cell death following dexamethasone treatment. We showed that an early accumulation of c-fos, c-jun and c-myc mRNA occurred in both phenomena but with different kinetics. It can be speculated that the early induction of nuclear oncogenes is necessary to allow the later induction of other genes probably regulated at the transcriptional level by the AP-1 complex and/or by Myc protein. The accumulation of the transcript for another gene, i.e. poly(ADP-ribose)polymerase, an enzyme responsible for posttranslational modifications of several nuclear proteins, could instead be related to chromatin modifications occurring in both processes.

Animals↗
PubMed1992

Inhibition of apoptosis by zinc: a reappraisal.

Apoptosis--or programmed cell death--is an active type of cell death, occurring in several pathophysiological conditions. One of the most important characteristics of apoptosis is that cell death is preceded by DNA fragmentation, consequent to the activation of nuclear calcium- and magnesium-dependent endonuclease(s). DNA fragmentation can be inhibited by zinc ions. By using several techniques, such as DNA agarose gel electrophoresis, cytofluorimetric analysis of DNA content and of cell cycle, 3H-thymidine incorporation and trypan blue dye exclusion test, we show that zinc, despite completely inhibiting DNA fragmentation and the consequent loss of nuclear DNA content, does not protect rat thymocytes from spontaneous or dexamethasone-induced death. Our data also suggest that DNA fragmentation, although characteristic, is not a critical event for thymocyte death of apoptotic type.

Animals↗
PubMed1992

Apoptosis--programmed cell death: a role in the aging process?

Cells continuously exposed to genotoxic agents, such as oxygen free radicals (OFRs), deeply involved in the aging process use a variety of cellular defense mechanisms. These defense mechanisms include DNA repair enzymes, antioxidants, poly(ADP-ribosyl)polymerase (pADPRP), and stress proteins and they constitute an integrated network. An age-related failure of the efficiency of this network can affect cell proliferation and cell death, two phenomena tightly linked and regulated. Recent data from our laboratory on the role of DNA damage and pADPRP activation and on the type of cell death induced by OFRs in human lymphocytes are reviewed. In vitro and in vivo data on possible strategies to reduce oxidative stress in lymphocytes from normal and Down syndrome subjects, by using natural compounds and trace elements, are presented. They indicate that nicotinamide and L-carnitine protect human cells from OFR-induced damage and suggest that they are possible candidates as antiaging substances.

Aging↗
PubMed1991

Studies on the relationship between cell proliferation and cell death: opposite patterns of SGP-2 and ornithine decarboxylase mRNA accumulation in PHA-stimulated human lymphocytes.

To assess the relationship between cell proliferation and cell death, the mRNA accumulation of ornithine decarboxylase (ODC) and sulfated glycoprotein 2 (SGP-2) were measured in human peripheral blood lymphocytes (HPBL) 2-6 hours after stimulation with phytohemagglutinin (PHA). ODC is the rate limiting enzyme of polyamines biosynthesis and its early induction in mitogen-stimulated lymphocytes has been reported. On the other hand, SGP-2, a glycoprotein present in most mammalian tissues, is induced in classical models of apoptosis, such as dexamethasone-treated thymocytes. Indeed, a consistent amount of SGP-2 mRNA in quiescent HPBL, an early and progressive decrease of SGP-2 mRNA and a parallel increase of ODC mRNA accumulation, were observed, in PHA-stimulated HPBL, suggesting that concomitant repression of SGP-2 and induction of ODC genes contribute for the cell entering the cell cycle.

Blotting, Northern↗
PubMed1991

In vivo accumulation of sulfated glycoprotein 2 mRNA in rat thymocytes upon dexamethasone-induced cell death.

Two hours after a single intraperitoneal injection of dexamethasone (20 micrograms/Kg b.w.) into adult male rats, a typical ladder of DNA fragments was detectable upon separation on agarose gels of DNA from thymocytes. This became maximally evident at 4 hours. Accumulation of sulfated glycoprotein-2 (SGP-2) mRNA, whose rate of expression has been associated to the processes of programmed cell death, preceded the appearance of DNA degradation, starting to increase as early as 30 min after steroid injection, and maintained higher than controls until 8 hrs; a different time course was shown by changes in the levels of beta-actin mRNA. In the spleen, under the same conditions, the SGP-2 message also increased at 30 min, prior to DNA fragmentation, but decreased thereafter below the control value.

Animals↗
PubMed1989

Philadelphia-positive chronic myelogenous leukemia with typical bcr/abl molecular features and atypical, prolonged survival.

Despite the major breakthrough in the knowledge of the molecular events underlying the t(9;22) translocation, still no consistent data have been found on the evolution of Ph1 positive CML from the chronic to the accelerated or blastic phase of the disease. In most patients in fact the bcr/abl rearrangements are identical both in chronic phase and in blast crisis, and overall differences in chronic phase duration, related to different location of breakpoints inside the bcr region, were found to be marginal. We approached this problem by studying the molecular features of the bcr/abl abnormality in rare CML patients with very long, atypical chronic phase. The three patients studied, whose chronic phase duration is 17, 19, and 21 years, respectively, have typical genomic bcr rearrangements, and two of them show, hybridizing Northern blots to c-abl, the 8.5 kb mRNA, as that typically present in CML. It seems that genomic alterations within bcr and abl cannot account, alone, for the duration of the chronic phase of Ph1 positive CML and those quantitative and/or qualitative alterations of the p210 bcr/abl protein, unluckily awkward to prove, might be responsible for the atypical clinical features of these CML long survivors.

Adult↗
PubMedDate not supplied

[Polymerase chain reaction for the diagnostic identification of HIV infection].

The Acquired Immune deficiency Syndrome (AIDS), caused by the Human Immunodeficiency Virus (HIV) is now a worldwide social problem. Routine diagnostic procedures to identify infected individuals are based on the presence of antibodies against viral epitopes in the serum. There is nevertheless impelling need to detect directly the virus in people infected by HIV, independently of a serological response. In this study we describe the procedure which allows amplification of a specific segment of the HIV genome, through the Polymerase Chain Reaction (PCR), in infected individuals. This new approach represents a precious tool towards the diagnosis of HIV infection, it can be easily and quickly carried out on a large scale and will be capable of identifying HIV infected subjects before the development of antibodies.

Acquired Immunodeficiency Syndrome↗