Biomedical subjects

Luciano D'Agostino

Publications and source records attributed to Luciano D'Agostino.

4 recordsLinked to original sources

PubMed2006

Nuclear aggregates of polyamines.

Nuclear aggregates of polyamines (NAPs) are cyclic supramolecular compounds made of polyamines and phosphate groups. Three different aggregates, s-NAP, m-NAP and l-NAP, with a molecular weight of 1035, 5175 and 9552 Da, respectively, are described. These molecules interact with genomic DNA. In consequence of this interaction, NAPs not only protect DNA from nucleases with extraordinarily greater efficiency than single polyamines (spermine, spermidine and putrescine), but also induce noticeable changes in DNA condensation status, as shown by temperature-dependent modifications of DNA electrophoretic properties. The biochemical characterization of these compounds has allowed the definition of a structural model for each NAP. According to this model, five s-NAPs assemble together to form a m-NAP unit. We hypothesize that the complexation of s-NAP into m-NAP favours the transition to Z-DNA through the progressive widening of DNA strands and the exposure of bases. We propose that NAPs, by wrapping the DNA helixes, form supramolecular tunnel-like structures that confer efficient protection without affecting DNA elasticity.

Cell Nucleus↗

PubMed2005

Nuclear aggregates of polyamines are supramolecular structures that play a crucial role in genomic DNA protection and conformation.

In a previous study we showed that natural polyamines interact in the nuclear environment with phosphate groups to form molecular aggregates [nuclear aggregates of polyamines (NAPs)] with estimated molecular mass values of 8000, 4800 and 1000 Da. NAPs were found to interact with genomic DNA, influence its conformation and interfere with the action of nucleases. In the present work, we demonstrated that NAPs protect naked genomic DNA from DNase I, whereas natural polyamines (spermine, spermidine and putrescine) fail to do so. In the context of DNA protection, NAPs induced noticeable changes in DNA conformation, which were revealed by temperature-dependent modifications of DNA electrophoretic properties. In addition, we presented, for NAPs, a structural model of polyamine aggregation into macropolycyclic compounds. We believe that NAPs are the sole biological forms by which polyamines efficiently protect genomic DNA against DNase I, while maintaining its dynamic structure.

Cell Nucleus↗

PubMed2003

Increased IGF-I : IGFBP-3 ratio in patients with hepatocellular carcinoma.

BACKGROUND: The development of hepatocellular carcinoma in liver cirrhosis is associated with altered synthesis and secretion of several growth factors. AIM: The aim of this prospective study was to investigate the potential implication of IGF-I and its major binding protein (IGFBP-3) in the development of hepatocellular carcinoma. PATIENTS AND METHODS: IGF-I and IGFBP-3 were measured in 150 healthy subjects, 40 patients with liver cirrhosis and 63 with liver cirrhosis and untreated hepatocellular carcinoma. The ratio between IGF-I and IGFBP-3 was also calculated. RESULTS: Serum IGF-I (70 +/- 10 and 65 +/- 7 vs. 185 +/- 6.4 microg/l, P < 0.001) and IGFBP-3 levels (1225 +/- 113 and 984 +/- 67 vs. 3017 +/ -80 microg/l, P < 0.001) were lower in patients with liver cirrhosis, without or with hepatocellular carcinoma, than in controls. Age was negatively correlated with IGF-I levels in patients with liver cirrhosis (r = -0.6; P = 0.0002) as well as in controls (r = -0.8, P < 0.0001), but not in patients with hepatocellular carcinoma (r = -0.2; P = 0.2). Additionally, in patients with liver cirrhosis (r = -0.54; P = 0.0003) and more weakly in those with hepatocellular carcinoma (r = -0.24; P = 0.04) IGF-I levels were negatively correlated with liver failure measured according with Child class. Despite patients with class C hepatocellular carcinoma being older than those in the same functional class with cirrhosis (64 +/- 2 vs. 57 +/- 12 years, P < 0.01), they had a significantly increased IGF-I : IGFBP-3 ratio (0.18 +/- 0.05 vs. 0.41 +/- 0.09, P = 0.04), due mostly to increased IGF-I levels (27.1 +/- 5.6 vs. 42 +/- 6.2 microg/l) as IGFBP-3 levels were similar to patients with cirrhosis (734 +/- 81 vs. 679 +/- 83 microg/l). CONCLUSIONS: Hepatocellular carcinoma is associated with a higher IGF-I : IGFBP-3 ratio than that found in patients with liver cirrhosis and a similar degree of liver failure.

Adult↗

PubMed2002

Polyamines interact with DNA as molecular aggregates.

New compounds, named nuclear aggregates of polyamines, having a molecular mass of 8000, 4800 and < 1000 Da, were found in the nuclear extracts of several replicating cells. Their molecular structure is based on the formation of ionic bonds between polyamine ammonium and phosphate groups. The production of the 4800 Da compound, resulting from the aggregation of five or more < 1000 Da units, was increased in Caco-2 cells treated with the mitogen gastrin. Dissolving single polyamines in phosphate buffer resulted in the in vitro aggregation of polyamines with the formation of compounds with molecular masses identical to those of natural aggregates. After the interaction of the 4800 Da molecular aggregate with the genomic DNA at 37 degrees C, both the absorbance of DNA in phosphate buffer and the DNA mobility in agarose gel increased greatly. Furthermore, these compounds were able to protect the genomic DNA from digestion by DNase I, a phosphodiesterasic endonuclease. Our data indicate that the nuclear aggregate of polyamines interacts with DNA phosphate groups and influence, more efficaciously than single polyamines, both the conformation and the protection of the DNA.

Adenocarcinoma↗