PubMed Health⌕ Search

Biomedical subjects

M A Zoroddu

Publications and source records attributed to M A Zoroddu.

10 recordsLinked to original sources
PubMed2004

Nickel(II) binding to Cap43 protein fragments.

Cap43 protein has been tested for metal binding domains. The protein, specifically induced by nickel compounds in cultured human cells, had a new mono-histidinic motif consisting of 10 amino acids repeated three times in the C-terminus. The 20-Ac-TRSRSHTSEG-TRSRSHTSEG (Thr(341)-Arg-Ser-Arg-Ser-His(346)-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser-His(356)-Thr-Ser-Glu-Gly(360) - peptide 1) and the 30-Ac-TRSRSHTSEG-TRSRSHTSEG-TRSRSHTSEG (Thr(341)-Arg-Ser-Arg-Ser-His(346)-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser-His(356)-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-Ser-His(366)-Thr-Ser-Glu-Gly(370) - peptide 2) amino acids sequence has been analyzed as a site for Ni(II) binding. A combined pH-metric and spectroscopic (UV-visible, CD, NMR) studies of Ni(II) binding to both fragments were performed. The 20-amino acid peptide can bind one and two metal ions while the 30-amino acid fragment one, two and three metal ions. At physiological pH, depending on the metal to ligand molar ratio, peptide 1 forms the Ni(2)L species while peptide 2 the NiL, Ni(2)L and Ni(3)L complexes where each metal ion is coordinated to the imidazole nitrogen atom of the histidine residue of the 10-amino acid fragment. Octahedral complexes at pH 8-9 and planar 4N complexes with (N(Im), 3N(-)) bonding mode at pH above 9, are formed. This work supports the existence of an interesting binding site at the COOH-terminal domain of the Cap43 protein.

Amino Acid Motifs↗
PubMed2002

Molecular mechanisms of nickel carcinogenesis.

Humans are exposed to carcinogenic nickel (Ni) compounds both occupationally and environmentally. In this paper, molecular mechanisms of nickel carcinogenesis are considered from the point-of-view of the uptake of nickel sulfide particles in cells, their dissolution and their effects on heterochromatin. Molecular mechanisms by which nickel induces gene silencing, DNA hypermethylation and inhibition of histone acetylation, will be discussed.

Acetylation↗
PubMed2001

Ni(II) and Cu(II) binding with a 14-aminoacid sequence of Cap43 protein, TRSRSHTSEGTRSR.

The tetradecapeptide containing the 10 aminoacid repeated sequence on the C-terminus of the Ni(II)-induced Cap43 protein, was analyzed for Ni(II) and Cu(II) binding. A combined pH-metric and spectroscopic UV-VIS, EPR, CD and NMR study of Ni(II) and Cu(II) binding to the blocked CH3CO-Thr-Arg-Ser-Arg-Ser-His-Thr-Ser-Glu-Gly-Thr-Arg-Ser-Arg-NH2 (Ac-TRSRSHTSEGTRSR-Am) peptide, modeling a part of the C-terminal sequence of the Cap43 protein, revealed the formation of octahedral complexes involving imidazole nitrogen of histidine, at pH 5.5 and pH 7 for Cu(II) and Ni(II), respectively; a major square planar 4N-Ni(II) complex (about 100% at pH 9, log K* = -28.16) involving imidazole nitrogen of histidine and three deprotonated amide nitrogens of the backbone of the peptide was revealed; a 3N-Cu(II) complex (maximum about 70% at pH 7, log K*=-13.91) and a series of 4N-Cu(II) complexes starting at pH 5.5 (maximum about 90% at pH 8.7, log K* = -21.39 for CuH(-3)L), were revealed. This work supports the existence of a metal binding site at the COOH-terminal part of the Cap43 peptide.

Amino Acid Sequence↗
PubMed2000

Interaction of Ni(II) and Cu(II) with a metal binding sequence of histone H4: AKRHRK, a model of the H4 tail.

Chromatin proteins are believed to represent reactive sites for nickel binding. The unique structure of the N-terminal tail of histone H4 contains sites for post-translational modification close to a histidine residue capable of anchoring binding sites for metal ions. We have analyzed as a minimal model for the H4 tail, the blocked peptide CH(3)CO-AKRHRK-CONH(2) for nickel and copper binding. Ultraviolet-visible, circular dichroism, electron paramagnetic resonance and nuclear magnetic resonance spectroscopic analysis showed that histidine acts as an anchoring metal binding site. A 1N complex is formed between pH=5-7 and 4-6 for Ni(II) and Cu(II), respectively, while at a higher pH a series of 4N complexes are formed. Above pH 8, the 2N high-spin octahedral resulted in a 4N low-spin planar Ni(II) complex. The stability constants of the Cu(II) (3N, 4N) and Ni(II) (4N) complexes with the peptide model of the H4 were distinctly higher than those for a similar blocked peptide with a histidine in the fourth position. Significant shifts in the alphaproton region in the 1H NMR spectrum of the 4N Ni-complex showed that the conformation of the peptide had been dramatically affected following Ni(II) complexation.

Amino Acid Sequence↗
PubMed1998

Enrichment with a polyunsaturated fatty acid enhances the survival of Saccharomyces cerevisiae in the presence of tributyltin.

The toxicity of inorganic metal species towards Saccharomyces cerevisiae has been shown to be markedly dependent on cellular fatty acid composition. In this investigation, the influence of fatty acid supplementation on the toxicity of the lipophilic organometal, tributyltin was investigated. Growth of S. cerevisiae was increasingly inhibited when the tributyltin concentration was increased from 0 to 10 microM. However, the inhibitory effect was partly alleviated by supplementation of the medium with 1 mM linoleate (18:2), a treatment that leads to large-scale incorporation of this polyunsaturated fatty acid (to > 60% of total fatty acids) in yeast membrane lipids. Cells that were previously enriched with 18:2 also showed reduced loss of vitality compared to cells grown in the absence of a fatty acid supplement, when exposed to tributyltin. For example, addition of tributyltin to a concentration of 0.1 microM was associated with an approximate 10% reduction in the H+ efflux activity of 18:2-enriched cells, but a 70% reduction in that of fatty acid-unsupplemented cells. Despite the increased tributyltin resistance of 18:2-enriched S. cerevisiae, the level of cell-associated tributyltin was found to be approximately two-fold higher in these organisms than in fatty acid-unsupplemented cells. These results demonstrate an increased resistance of 18:2-enriched membranes to the direct toxic action(s) of tributyltin. This is in contrast to the previously reported effect of 18:2 enrichment on sensitivity of S. cerevisiae to inorganic metal cations.

Culture Media↗
PubMed1997

A novel dimeric oxovanadium (IV) species identified in Saccharomyces cerevisiae cells.

Saccharomyces cerevisiae cells stored oxovanadium (IV) ions in a dimeric form. In the late stationary phase Saccharomyces cerevisiae cells grown in rich medium containing concentrations of oxovanadium (V), orthovanadate from 12 to 18 mM, causing growth stasis, a dimeric oxovanadium (IV) species was identified by EPR spectroscopy. The EPR spectrum exhibited at 110 K the low-field forbidden deltaMs = +/-2 transition at g around 4 and the half-field deltaMs = +/-1 15-lines feature at g around 2 out of the presence of a triplet state by the coupling of the oxovanadium (IV) ions in a dimeric form. Hyperfine splitting of 75.2 x 10(-4) cm(-1) and an interionic distance of about 4.4 angstroms was calculated. The dimeric species was localized in the cellular cytoplasmic space.

Culture Media↗
PubMed1997

Vanadium affects vacuolation and phosphate metabolism in Hansenula polymorpha.

The yeast Hansenula polymorpha is able to grow on vanadate concentrations that are toxic to other organisms. Transmission electron microscopy analysis showed that H. polymorpha cells growing on a vanadate-containing medium undergo a significant increase in cell vacuolation and a thickening of the cell wall; the presence of small cytoplasmic vesicles and an increase in cristae at the level of the plasma membrane were also observed. These ultrastructural modifications were accompanied by a change in the intracellular polyphosphate level, as shown by in vivo 31P-NMR. The involvement of these observed changes in vanadium detoxification is discussed.

Cell Division↗
PubMed1996

Electron paramagnetic resonance studies and effects of vanadium in Saccharomyces cerevisiae.

Vanadium uptake by whole cells and isolated cell walls of the yeast Saccharomyces cerevisiae was studied. When orthovanadate was added to wild-type S. cerevisiae cells growing in rich medium, growth was inhibited as a function of the VO4(3-) concentration and the growth was completely arrested at a concentration of 20 mM of VO4(3-) in YEPD. Electron paramagnetic resonance (EPR) spectroscopy was used to obtain structural and dynamic information about the cell-associated paramagnetic vanadyl ion. The presence of EPR signals indicated that vanadate was reduced by whole cells to the vanadyl ion. On the contrary, no EPR signals were detected after interaction of vanadate with isolated cell walls. A 'mobile' and an 'immobile' species associated in cells with small chelates and with macromolecular sites, respectively, were identified. The value of rational correlation time tau r indicated the relative motional freedom at the macromolecular site. A strongly 'immobilized' vanadyl species bound to polar sites mainly through coulombic attractions was detected after interaction of VO2+ ions with isolated cell walls.

Cell Division↗
PubMed1996

An electron spin resonance study and antimicrobial activity of copper(II)-phenanthroline complexes.

The antimicrobial activities of some copper(II) binary complexes with unsubstituted and different substituted phenanthroline ligands were investigated. A considerable increase in the biocidal activity of the ligands on being coordinated with the copper(II) ions was observed in terms of their minimum inhibitory concentration (MIC) values. EPR measurements were performed at room and low temperature with the aim of gaining an insight into the structure/activity relationship of these complexes. Subtle differences in the chemical arrangement result in appreciable differences in the antimicrobial activity. Copper(II) complexes with 2,9-dimethyl derivative phenanthrolines were observed to be more active against Staphylococcus aureus and Escherichia coli.

Anti-Infective Agents↗