V O L .   5 2,   N. 2,   J U N E   2003

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FORUM
On the proposed reformation of university professorship in Italy (formato Acrobat)
A. Bellelli

SIB news (formato Acrobat)

The origin of dystrophin-glycoprotein complex(DGC)-related muscular dystrophies: the need for protection against an ancestral pathogen?

A. Brancaccio

The Italian Journal of Biochemistry: 2003; 52(2): 68-71

ABSTRACT. Because of its crucial role during the early stages of morphogenesis, no genetic defects associated to dystroglycan have been reported so far. Dystroglycan is an important member of the dystrophin-glycoprotein complex (DGC) and in several muscular dystrophies, depending on abnormalities of proteins belonging to or associated with the DGC, it is frequently observed a significant reduction of dystroglycan levels at the sarcolemma. Recently, it has been demonstrated that dystroglycan acts as a receptor for pathogens such as M. leprae and arenaviruses. It is well-known that mutated alleles causing diseases can be selected in order to confer an additional genetic advantage. Herein it is discussed the possibility that mutations leading to a certain number of muscular dystrophies might have been originally selected to indirectly gain a specific advantage: the absence or the lower levels of dystroglycan could have greatly reduced the risk of some ancestral lethal infections specifically directed against muscles.

Aminoacid profile and oxidative status in children affected by Down syndrome before and after supplementary nutritional treatment

M. Ciaccio, M. Piccione, M. Giuffrè, V. Macaione, L. Vocca, A. Bono, G. Corsello

The Italian Journal of Biochemistry: 2003; 52(2): 72-79

ABSTRACT. Down syndrome is the most common autosomal aberration among liveborns, characterised by several clinical features and metabolic disturbances. Aminoacid pathways abnormalities and defective oxidative balance are the most common metabolic problems in Down Syndrome. To evaluate the biochemical responses of children with Down Syndrome to a nutritional regimen supplemented with aminoacids, vitamins and polyunsaturated fatty acids, we submitted 86 subjects divided in two groups (0-6 and 6-12 years) to the dosage of plasma levels of aminoacids, antioxidant enzymes activities and reactive oxygen species, before and after 12 months of such nutritional supplementation and in relation to normal controls. The results obtained showed a tendency towards the values of normal subjects with statistically significant differences. Although other studies must be performed to confirm and define such report, our experience supports the usefulness of a nutritional supplementation with aminoacids, vitamins and polyunsaturated fatty acids, also considering the absence of side effects.

Biochemical characterization of human brain and kidney tissues by Magnetic Resonance Spectroscopy

V. Tugnoli, M.R. Tosi

The Italian Journal of Biochemistry: 2003; 52(2): 80-86

ABSTRACT. In vivo and in vitro Magnetic Resonance Spectroscopy is usefull for monitoring changes in intracellular metabolites of human cerebral and renal tissues. Healthy and tumoral tissues of different histologic types have been characterized from a biochemical point of view. In vitro molecular characterization is performed on both the aqueous and lipid extracts of surgically removed tissue biopsies, after in vivo MRS, yielding a full picture of tissue biochemistry. Biochemical markers of healthy brain and kidney and of their relative neoplastic lesions have been disclosed. Moreover, some biochemical features can differentiate neoplasm within the same histological type. Ex vivo MRS also gives molecular information related to necrotic phenomena in glial tumors. MRS finding paralleled histologic data and new knowledge about the molecular base of proliferative neoplastic phenomena can be obtained.

Vibrational characterisation and biological activity of Carnosine and its metal complexes

A. Torreggiani, A. Trinchero, M. Tamba, G. Fini

The Italian Journal of Biochemistry: 2003; 52(2): 87-97

ABSTRACT. The spectroscopic characterisation of free carnosine and its coordination compounds with Cu(II), Zn(II) and Co(II) ions are discussed. Raman and IR studies on metal-carnosine systems have been performed, obtaining a relationship between the vibrational spectra and the structure of the predominant species formed. The biological activity of free carnosine and of its complexes is briefly considered.

Imaging transcription complexes with the Atomic Force Microscope

C. Rivetti, N. Vannini, S. Cellai

The Italian Journal of Biochemistry: 2003; 52(2): 98-103

ABSTRACT. Recent developments in sample deposition and image analysis have shown that the Atomic Force Microscope is a valuable tool for the structural investigation of transcription complexes. When deposited under conditions that allow molecular equilibration onto the substrate, transcription complexes behave as worm-like chains and the mean square end-to-end distance can readily be used to determine the protein induced DNA bend angle. Measurements of the DNA contour length by means of accurate image processing procedures have revealed a DNA compaction in transcription complexes which is compatible with wrapping of the DNA against the surface of the RNA Polymerase. The methods presented have to be considered of general practical use for imaging protein-DNA complexes.

Oogenesis in Drosophila melanogaster: a model system for studying cell differentiation and development

S. Gigliotti, D. Rotoli, F. Graziani, C. Malva

The Italian Journal of Biochemistry: 2003; 52(2): 104-111

ABSTRACT. Drosophila oogenesis is a complex developmental process involving the coordinated differentiation of germ line and somatic cells. Correct execution and timing of cell fate specification and patterning events is achieved during this process by the integration of different cell-cell signalling pathways, eventually leading to the generation of positional information inside the oocyte, that is instrumental for the establishment of embryonic polarity. The large body of data accumulated at both cellular and molecular levels in the last decade clearly demonstrated how Drosophila oogenesis is a genetically tractable system particularly suited for the investigation of key developmental biology questions. Our recent contribution to the field relies on the characterisation of three different mutants named tegamino (teg), hold hup (hup) and tulipano (tlp), identifying novel gene functions required during oogenesis. Specifically, teg is implicated in the morphogenesis of the follicular epithelium surrounding the germ line cells in the egg chamber, hup is involved in the establishment of egg chamber polarity and tlp in the regulation of the dynamic germ cell chromatin organisation.

Apoptosis meets proteasome, an invaluable therapeutic target of anticancer drugs

M. Giuliano, A. D'Anneo, A. De Blasio, R. Vento, G. Tesoriere

The Italian Journal of Biochemistry: 2003; 52(2): 112-121

ABSTRACT. This report reviews the current status of extensive efforts directed towards the interpretation of crosstalk between apoptosis and proteasome to understanding the molecular mechanism of anticancer agents targeting proteasome, with particular focus on MG132 and PS-341. The discovery that all cancer cells have retained the apoptotic death program has offered to the researchers new biochemical targets to design anticancer drugs. Moreover, the demonstration that proteasome inhibition induces apoptosis and sensitizes cancer cells to traditional tumoricidal agents has proposed the proteasome as an attractive target for development of new anticancer drugs. Since then, a number of both naturally occurring and synthetic inhibitors of the proteasome have been identified. The best characterized and most widely used inhibitors of the proteasome are the peptide aldehydes; among these MG132, due to its broad spectrum of action, low cost and rapid reversibility of action, still remains the first choice to study proteasome function in cell and tissue cultures. Recently, a very potent new class of selective and reversible proteasome inhibitors which contains an inhibitory boronate group has been described. PS-341 represent the first of this promising class of agents that could have application in cancer therapy and it is the only that has progressed to clinical trials.

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