on by retinoids are included the activation of mitogen-activated protein kinases (MAPK) (Canon et al 2004) phosphatidylinositol-3-kinase (PI3 K) and Akt (Canon et al 2004; Masia et al 2007) Src non-receptor tyrosine kinase (Gelain et al 2006) and modulation of protein kinase C (PKC) activity (Miloso et al 2004) Due to its ability to scavenge free radicals and related species retinol was considered an important antioxidant component of diet Supplementation with retinol was suggested to exert preventive actions against ROS-related diseases such as cancer and the effect of retinoids as adjuvant in experimental therapies was also studied (Mongan and Gudas 2007).

However clinical trials and epidemiologic studies reported that supplementation with retinol or other derivatives actually increased the incidence of diseases associated with oxidative stress such as cancer and cardiovascular diseases (Omenn et al 1991 1996; The Vinorelbine ABC-Cancer Prevention Study Group 1994) Indeed specific concentrations of retinol increase ROS production in cell cultures causing damage to lipids and DNA and activating cell signaling pathways associated to cell death and pre-neoplasic transformation such as the ERK1/2 MAPK and PKC (Dal-Pizzol et al 2000; Gelain et al 2006 2007) The receptor for advanced glycation end-products (RAGE) is a membrane protein belonging to the immunoglobulin family of proteins RAGEs were first characterized in diabetes where the gradual accumulation of advanced glycation end-products (AGE) was observed to trigger signaling responses inside cells (Yan et al 1997) These responses included gene expression modulation free radicals production and release of pro-inflammatory cytokines that ultimately enhance many of the complications related to Linifanib this disease (Lukic et al 2008; Maczurek et al 2008) .

RAGE activation is involved in the promotion of either cell death or survival depending on cell type and experimental conditions This dual function of RAGE is essential during supplier Fesoterodine development when a fine control of cell proliferation and apoptosis is needed In adult life RAGE is downregulated but its expression may be enhanced by inflammatory mediators or accumulation of RAGE ligands (Bopp et al 2008) RAGE activation also triggers its own upregulation resulting in intensification of free radical production and expression of pro-inflammatory mediators Modulation of RAGE expression and activation is believed for these reasons to rely on the cellular mechanisms of toxicity bullet exerted by different endogenous compounds such as beta-amyloid peptide or exogenous agents such as several glycated proteins (Creagh-Brown et al 2010) .

Sertoli cells are physiological targets for retinol and retinoic acid and for this reason order Bortezomib constitute a suitable model to study cellular functions of vitamin A since a variety of reproductive-related processes are regulated by RAR/RXR receptors in a constitutive fashion in these cells (Hogarth and Griswold 2010) We previously observed that Sertoli cells treatement.