Rabbit Anti-Human SLC7A5 Polyclonal antibody

The supply of L-carnosine, a bioactive dipeptide of beta-alanine and L-histidine, to the retina across the blood-retinal barrier (BRB) was studied. The in vivo and in vitro studies revealed low uptake activities for [H-3]Gly-Sar, a representative dipeptide, suggesting that L-carnosine transport plays only a minor role at the BRB. The in vivo study using rats showed approximately 18- and 23-fold greater retinal uptake indexes (RUI) for [H-3]beta-alanine and [H-3]L-histidine compared with that of a paracellular marker, respectively. The RUI of [H-3]beta-alanine was taurine- and gamma-aminobutyric acid-sensitive, and the in vitro uptake by TR-iBRB2 cells showed time- concentration- and temperature-dependent [H-3]beta-alanine uptake, suggesting that a carrier-mediated process was involved in beta-alanine transport across the inner BRB. [H-3]beta-Alanine uptake was inhibited by taurine and beta-guanidinopropionic acid, suggesting that taurine transporter (TAUT/SLC6A6) is responsible for the influx transport of beta-alanine across the inner BRB. Regarding L-histidine, the L-leucine-sensitive RUI of [H-3]L-histidine was identified, and the in vitro [H-3]L-histidine uptake by TR-iBRB2 cells suggested that a carrier-mediated process was involved in L-histidine transport across the inner BRB. The inhibition profile suggested that L-type amino acid transporter (LAT1/SLC7A5) is responsible for the influx transport of L-histidine across the inner BRB. These results show that the influx transports of beta-alanine and L-histidine across the inner BRB is carried out by TAUT and LAT1, respectively, suggesting that the retinal L-carnosine is supplied by enzymatic synthesis from two kinds of amino acids transported across the inner BRB. (C) 2013 Elsevier Ltd. All rights reserved.

Cytotoxic activities of several Golgi-dispersing compounds including AMF-26/M-COPA, brefeldin A and golgicide A have previously been shown to induce autophagy or apoptosis. Here, we demonstrate that these Golgi disruptors also trigger ferroptosis, a non-apoptotic form of cell death characterized by iron-dependent oxidative degradation of lipids. Inhibitors of ferroptosis not only counteract cell death, but they also protect from Golgi dispersal and inhibition of protein secretion in response to several Golgi stress agents. Furthermore, the application of sublethal doses of ferroptosis-inducers such as erastin and sorafenib, low cystine growth conditions, or genetic knockdown of SLC7A11 and GPX4 all similarly protect cells from Golgi stress and lead to modulation of ACSL4, SLC7A5, SLC7A11 or GPX4 levels. Collectively, this study suggests a previously unrecognized function of the Golgi apparatus, which involves cellular redox control and prevents ferroptotic cell death.