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Naldi M.,Centro Interdipartimentale Of Ricerche Biotecnologiche | Giannone F.A.,Centro Of Ricerca Biomedica Applicata Crba | Giannone F.A.,University of Bologna | Baldassarre M.,Centro Of Ricerca Biomedica Applicata Crba | And 8 more authors.
European Journal of Mass Spectrometry | Year: 2013

A relatively fast analytical method for the identification and quantification of the post-transcriptional changes (PTCs) occurring in circulating human serum albumin (HSA) was developed. HSA is the most abundant protein in plasma and it represents the main determinant of plasma oncotic pressure, thus being the main modulator of fluid distribution between body compartments. Cirrhotic patients have low levels of HSA. Moreover, recent studies have demonstrated that during liver cirrhosis HSA presents PTCs affecting its properties. The HSA isoforms derived from these modifications could represent promising biomarkers for liver disease. Human plasma samples were collected from a cirrhotic patient (CH) and from an aged-matched non-cirrhotic subject (CT), purified by reverse-phase chromatography and analysed by an electrospray ionization quadrupole time-of-flight (ESI-Q-ToF) spectrometer. The deconvoluted ESI mass spectra from healthy subjects were all characterized by peaks attributed to mercaptoalbumin, nitrosylated, cysteinylated, glycated and N-terminal truncated HSA isoforms. The relative abundance of each isoform was derived and transformed into a relative per cent amount and the results were compared to those obtained analysing HSA from a CH plasma. The method was validated in terms of intra-day and inter-day reproducibility, both for quantitative results and PTCs molecular weight determination. The optimized method resulted in being effective in disclosing changes in HSA isoforms relative abundance and then it could be used for the systematic screening of cirrhotic patients to identify promising new biomarkers for liver diseases. © IM Publications LLP 2013 All rights reserved.

Montanaro L.,University of Bologna | Calienni M.,University of Bologna | Bertoni S.,University of Bologna | Rocchi L.,University of Bologna | And 14 more authors.
Cancer Research | Year: 2010

In up to 60% of human cancers, p53 gene mutations are responsible for direct inactivation of the tumor suppressor function of p53. Alternative mechanisms of p53 inactivation described thus far mainly affect its posttranslational regulation. In X-linked dyskeratosis congenita, a multisystemic syndrome characterized by increased cancer susceptibility, mutations of the DKC1 gene encoding dyskerin cause a selective defect in the translation of a subgroup of internal ribosome entry site (IRES)-containing cellular mRNAs. In this study, we show that impairment of dyskerin function can cause p53 inactivation due to a defect in p53 mRNA translation. siRNA-mediated reduction of dyskerin levels caused a decrease of p53 mRNA translation, protein levels, and functional activity, both in human breast cancer cells and in primary mammary epithelial progenitor cells. These effects seemed to be independent of the known role of dyskerin in telomerase function, and they were associated with a specific impairment of translation initiation mediated by IRES elements present in p53 mRNA. In a series of human primary breast cancers retaining wild-type p53, we found that low levels of dyskerin expression were associated with reduced expression of p53-positive target genes. Our findings suggest that a dyskerin-mediated mechanism of p53 inactivation may occur in a subset of human tumors. ©2010 AACR.

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