Search

Abstract: Proteasome inhibitors exhibit antitumoral activity against malignancies of different histology. Emerging evidence indicates that antiapoptotic factors may also accumulate as a consequence of exposure to these drugs, thus it seems plausible that activation of survival signaling cascades might compromise their antitumoral effects. Bcl-2-associated athanogene (BAG) family proteins are characterized by their property of interaction with a variety of partners involved in modulating the proliferation/death balance, including heat shock proteins (HSP), Bcl-2, Raf-1. In this report, we demonstrated that BAG3 is a novel antiapoptotic molecule induced by proteasome inhibitors in various cancer cells at the transcriptional level. Moreover, we demonstrated that BAG3 knockdown by siRNA sensitized cancer cells to MG132-induced apoptosis. Taken together, our results suggest that BAG3 induction might represents as an unwanted molecular consequence of utilizing proteasome inhibitors to combat tumors. [Copyright &y& Elsevier]

Nephrogenesis requires a fine balance of many factors that can be disturbed by intrauterine growth restriction (IUGR), leading to a low nephron endowment. The aim of this study was to test the hypothesis that IUGR affects expression of key proteins that regulate nephrogenesis, by a comparative proteomic approach. IUGR was induced in Sprague–Dawley (SD) rats by isocaloric protein restriction in pregnant dams. A series of methods, including two-dimensional gel electrophoresis (2-DE), silver staining, mass spectrometry and database searching was used. After silver staining, 2-DE image analysis detected an average 730 ± 58 spots in the IUGR group and 711 ± 73 spots in the control group. The average matched rate was 86% and 81%, respectively. The differential proteomic expression analysis found that 11 protein spots were expressed only in the IUGR group and one in the control group. Seven protein spots were up-regulated more than fivefold and two were down-regulated more than fivefold in the IUGR group compared with those in control group. These 21 protein spots were preliminarily identified and were structural molecules, including vimentin, perlecan, gamma-actin and cytokeratin 10, transcription regulators, transporter proteins, enzymes, and so on. These proteins were involved primarily in energy metabolism, oxidation and reduction, signal transduction, cell proliferation and apoptosis. Data from this study may provide, at least partly, evidence that abnormality of metabolism, imbalance of redox and apoptosis, and disorder of cellular signal and cell proliferation may be the major mechanisms responsible for abnormal nephrogenesis in IUGR. [ABSTRACT FROM AUTHOR]