amsonic-acid and hydroxide-ion

The SLC4A11 gene mutations cause a variety of genetic corneal diseases, including congenital hereditary endothelial dystrophy 2 (CHED2), Harboyan syndrome, some cases of Fuchs' endothelial dystrophy (FECD), and possibly familial keratoconus. Three NH2-terminal variants of the human SLC4A11 gene, named SLC4A11-A, -B, and -C are known. The SLC4A11-B variant has been the focus of previous studies. Both the expression of the SLC4A11-C variant in the cornea and its functional properties have not been characterized, and therefore its potential pathophysiological role in corneal diseases remains to be explored. In the present study, we demonstrate that SLC4A11-C is the predominant SLC4A11 variant expressed in human corneal endothelial mRNA and that the transporter functions as an electrogenic H(+)(OH(-)) permeation pathway. Disulfonic stilbenes, including 4,4'-diisothiocyano-2,2'-stilbenedisulfonate (DIDS), 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonate (H2DIDS), and 4-acetamido-4'-isothiocyanato-stilbene-2,2'-disulfonate (SITS), which are known to bind covalently, increased SLC4A11-C-mediated H(+)(OH(-)) flux by 150-200% without having a significant effect in mock-transfected cells. Noncovalently interacting 4,4'-diaminostilbene-2,2'-disulfonate (DADS) was without effect. We tested the efficacy of DIDS on the functionally impaired R109H mutant (SLC4A11-C numbering) that causes CHED2. DIDS (1 mM) increased H(+)(OH(-)) flux through the mutant transporter by ∼40-90%. These studies provide a basis for future testing of more specific chemically modified dilsulfonic stilbenes as potential therapeutic agents to improve the functional impairment of specific SLC4A11 mutant transporters.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Anion Transport Proteins; Antiporters; Biological Transport; Cell Line; Cornea; Endothelial Cells; HEK293 Cells; Humans; Hydroxides; Mutation; Permeability; RNA, Messenger; Signal Transduction

Organic ultraviolet (UV) rays absorbents have been used as sunscreen materials, but they may pose a safety problem when used at high concentration. In order to prevent direct contact of organic UV rays absorbent to the human skin, a typical organic UV-absorbent, 4,4(')-diaminostilbene-2,2(')-disulfonic acid (DASDSA), was intercalated into Zn(2)Al layered double hydroxide (Zn(2)Al-LDH) by coprecipitation reaction. However, deintercalation of DASDSA from Zn(2)Al-LDH, by the anion exchange reaction with carbonate ion, was observed. Therefore, Zn(2)Al-LDH/DASDSA was directly coated with silica by means of polymerization technique based on the Stöber method. Silica coating effectively depressed the deintercalation of DASDSA from Zn(2)Al-LDH. The amorphous silica was confirmed by XRD, SEM, TEM and FT-IR. The deintercalation behaviors as well as UV-shielding properties were investigated for coated particles.

Topics: 4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; Hydrolysis; Hydroxides; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nanocomposites; Photochemistry; Silicon Dioxide; Spectroscopy, Fourier Transform Infrared; Stilbenes; X-Ray Diffraction