Anti-SLC4A4 (aa 121-229) polyclonal antibody

The synthetic compound N-cyanosulphonamide S0859 has been described as a selective inhibitor of sodium-bicarbonate cotransporters (NBC, SLC4) in mammalian heart (Ch'en et al., 2008). First, for comparison, the electrogenic human NBCe1 (SLC4A4) was heterologously expressed in Xenopus laevis oocytes, where its transport activity was inhibited by S0859 with an IC50 of 9 mu M. The activity of monocarboxylate transporter (MCT) isoforms 1, 2, and 4 (SLC16A1, SLC16A7, SLC16A3), which transport lactate, pyruvate and ketone bodies, were also heterologously expressed in Xenopus oocytes, and their transport activity was similarly and reversibly inhibited by S0859 with an IC50 of 4-10 mu M. Partial inhibition of lactate transport by S0859 (50 mu M) was also obtained in cultured astrocytes of mice. Thus, S0859 appears to be an inhibitor of anion transport with a broader spectrum than previously thought, and may also interfere with cellular metabolite uptake/release. (C) 2015 Elsevier B.V. All rights reserved.

Self-renewing neural stem cells and progenitor cells are cell populations that generate radial glial cells and neurons through asymmetric division. Regulation of intracellular pH in stem cells with high metabolic activity is critical for both cell signaling and proliferation. We have recently found that a S0859-inhibitable electrogenic Na+/HCO3- co-transporter (NBCe1, Slc4a4), is the primary pH(i) regulatory mechanism in stem cell-derived radial glial-like cells. Here we show, by using the voltage-sensitive fluorescent dye DiBAC 4(3) and BCECF, a pH-sensitive dye, that an antioxidant, tannic acid (100 mu M), can inhibit potassium- and calcium-dependent rapid changes in membrane potential and NBCe1 mediated pH i regulation in brain-derived glial-like cells in vitro. Furthermore, neural stem cell differentiation and neurosphere formation (proliferation) were completely inhibited by tannic acid. The present study provides evidence that tannic acid is a natural inhibitor of NBCe1. It is tempting to speculate that tannic acid or related compounds that inhibits NBCe1-mediated pH(i) regulation in glial-like cells may also have bearing on the treatment of glial neoplasms. NeuroReport 31: 57-63 Copyright (c) 2019 The Author(s). Published by Wolters Kluwer Health, Inc.