Glutathione limits Ero1-dependent oxidation in the endoplasmic reticulum

Many proteins of the secretory pathway contain disulfide bonds that are essential for structure and function. In the endoplasmic reticulum (ER), Ero1alpha and Ero1beta oxidize protein disulfide isomerase (PDI), which in turn transfers oxidative equivalents to newly synthesized cargo proteins. However, oxidation must be limited, as some reduced PDI is necessary for disulfide isomerization and ER-associated degradation. Here we show that in semipermeable cells, PDI is more oxidized, disulfide bonds are formed faster, and high molecular mass covalent protein aggregates accumulate in the absence of cytosol. Addition of reduced glutathione (GSH) reduces PDI and restores normal disulfide formation rates. A higher GSH concentration is needed to balance oxidative folding in semipermeable cells overexpressing Ero1alpha, indicating that cytosolic GSH and lumenal Ero1alpha play antagonistic roles in controlling the ER redox. Moreover, the overexpression of Ero1alpha significantly increases the GSH content in HeLa cells. Our data demonstrate tight connections between ER and cytosol to guarantee redox exchange across compartments: a reducing cytosol is important to ensure disulfide isomerization in secretory proteins

FRESHNESS QUALITY OF GILTHEAD SEA BREAM (Sparus aurata) REARED UNDER DIFFERENT FARMING CONDITIONS

Sensory and physico-chemical freshness indices (QI score, Torrymeter readings, pH and WHC) were evaluated in gilthead sea bream of commercial size reared in Italy in: land based facilities (recirculation systems), lagoons and net-cages. Fish were stored under ice for 0, 1, 3, 6, 9, 12 and 16 days: at each sampling time analyses were performed to determine the evolution of each freshness index within sea bream sources. Significant differences emerged among farming conditions following the application of the Quality Index Method. Torrymeter readings gradually decreased with the number of days of ice storage. pH values remained practically constant over the 16 days of storage. For WHC the effect of both time of storage and farming conditions was statistically significant

FRESHNESS QUALITY OF GILTHEAD SEA BREAM (Sparus aurata) REARED UNDER DIFFERENT FARMING CONDITIONS

Sensory and physico-chemical freshness indices (QI score, Torrymeter readings, pH and WHC) were evaluated in gilthead sea bream of commercial size reared in Italy in: land based facilities (recirculation systems), lagoons and net-cages. Fish were stored under ice for 0, 1, 3, 6, 9, 12 and 16 days: at each sampling time analyses were performed to determine the evolution of each freshness index within sea bream sources. Significant differences emerged among farming conditions following the application of the Quality Index Method. Torrymeter readings gradually decreased with the number of days of ice storage. pH values remained practically constant over the 16 days of storage. For WHC the effect of both time of storage and farming conditions was statistically significant

Proton pump inhibitor chemosensitization in human osteosarcoma: from the bench to the patients' bed.

BACKGROUND: Major goals in translational oncology are to reduce systemic toxicity of current anticancer strategies and improve effectiveness. An extremely efficient cancer cell mechanism to avoid and/or reduce the effects of highly cytotoxic drugs is the establishment of an acidic microenvironment, an hallmark of all malignant tumors. The H\u2009+-rich milieu that anticancer drugs meet once they get inside the tumor leads to their protonation and neutralization, therefore hindering their access into tumor cells. We have previously shown that proton pump inhibitors (PPI) may efficiently counterattack this tumor advantage leading to a consistent chemosensitization of tumors. In this study, we investigated the effects of PPI in chemosensitizing osteosarcoma. METHOD: MG-63 and Saos-2 cell lines were used as human osteosarcoma models. Cell proliferation after pretreatment with PPI and subsequent treatment with cisplatin was evaluated by using erythrosin B dye vital staining. Tumour growth was evaluated in xenograft treated with cisplatin after PPI pretreatment. Subsequently, a multi-centre historically controlled trial, was performed to evaluate the activity of a pre-treatment administration of PPIs as chemosensitizers during neoadjuvant chemotherapy based on methotrexate, cisplatin, and adriamycin. RESULTS: Preclinical experiments showed that PPI sensitize both human osteosarcoma cell lines and xenografts to cisplatin. A clinical study subsequently showed that pretreatment with PPI drug esomeprazole leads to an increase in the local effect of chemotherapy, as expressed by percentage of tumor necrosis. This was particularly evident in chondroblastic osteosarcoma, an histological subtype that normally shows a poor histological response. Notably, no significant increase in toxicity was recorded in PPI treated patients. CONCLUSION: This study provides the first evidence that PPI may be beneficially added to standard regimens in combination to conventional chemotherapy

RANCIDITY DEVELOPMENT DURING FROZEN STORAGE OF FILLETS FROM GILTHEAD SEABREAM (Sparus aurata) REARED IN ITALY

Lipid oxidation indices (Free Fatty Acids-FFA, Peroxide Value-PV and Thiobarbituric Acid-TBA) were evaluated in frozen fillets from seabream reared in Italy in: land based facilities (recirculation systems), lagoons or net-cages. Statistically significant differences emerged among seabream sources for all indices. Quality loss related to rancidity seemed to have been affected by both storage time and culturing system