Role of N-glycosylation in renal betaine transport.

The osmolyte and folding chaperone betaine is transported by the renal Na(+)-coupled GABA (γ-aminobutyric acid) symporter BGT-1 (betaine/GABA transporter 1), a member of the SLC6 (solute carrier 6) family. Under hypertonic conditions, the transcription, translation and plasma membrane (PM) insertion of BGT-1 in kidney cells are significantly increased, resulting in elevated betaine and GABA transport. Re-establishing isotonicity involves PM depletion of BGT-1.

Fluoride.

A recent conversation with a colleague prompted me to read this CPD article on fluoride. She told me my tea drinking might have health benefits in the form of increased fluoride intake.

Mutation of a single threonine in the cytoplasmic NH2 terminus disrupts trafficking of renal betaine-GABA transporter 1 during hypertonic stress.

Betaine is an important osmolyte and is, compared with other organs, much more abundant in the kidneys, where it enters cells in the medulla by betaine-GABA transporter 1 (BGT1) to balance osmoregulation in the countercurrent system. In wild-type (wt-)BGT1-expressing oocytes, GABA-mediated currents were diminished by preincubation of oocytes with 100 nM PMA or 5 μM dioctanoyl-sn-glycerol, activators of PKC, whereas the application of staurosporine before the application of dioctanoyl-sn-glycerol restored the response to GABA. Four potential phosphorylation sites on BGT1 were mutated to alanine by site-directed mutagenesis.

The betaine/GABA transporter and betaine: roles in brain, kidney, and liver.

The physiological roles of the betaine/GABA transporter (BGT1; slc6a12) are still being debated. BGT1 is a member of the solute carrier family 6 (the neurotransmitter, sodium symporter transporter family) and mediates cellular uptake of betaine and GABA in a sodium- and chloride-dependent process. Most of the studies of BGT1 concern its function and regulation in the kidney medulla where its role is best understood.

Betaine transport in kidney and liver: use of betaine in liver injury.

Betaine, also known as trimethylglycine, is an important human nutrient obtained from a variety of foods and also can be synthesized from choline. Betaine is much more abundant in kidney and liver compared to other mammalian organs. The principal role of betaine in the kidney is osmoprotection in cells of the medulla and it enters these cells via the betaine/γ-aminobutyric acid (GABA) transporter protein (BGT1), which is upregulated by hyperosmotic stress.

Morphological changes to endothelial and interstitial cells and to the extra-cellular matrix in canine myxomatous mitral valve disease (endocardiosis).

Morphological and functional changes in endothelial and interstitial cells are considered central to myxomatous degeneration of the canine mitral valve (endocardiosis). The aim of this study was to describe and quantify changes in valve endothelial cells (VECs), interstitial cells (VICs) and the extra-cellular matrix (ECM) of the sub-endothelial zone of diseased valves using a combination of transmission electron microscopy, stereology and computer-aided image analysis. Marked degradation of the endothelium was evident in diseased valves, which coincided with significant degradation of the local ECM (P<0.

The betaine-GABA transporter (BGT1, slc6a12) is predominantly expressed in the liver and at lower levels in the kidneys and at the brain surface.

The Na(+)- and Cl(-)-dependent GABA-betaine transporter (BGT1) has received attention mostly as a protector against osmolarity changes in the kidney and as a potential controller of the neurotransmitter GABA in the brain. Nevertheless, the cellular distribution of BGT1, and its physiological importance, is not fully understood. Here we have quantified mRNA levels using TaqMan real-time PCR, produced a number of BGT1 antibodies, and used these to study BGT1 distribution in mice.

Calcific tendonitis of the tibialis posterior tendon at the navicular attachment.

Calcific tendinosis (tendonosis/tendonitis) is a condition which results from the deposition of calcium hydroxyapatite crystals in any tendon of the body. Calcific tendonitis usually presents with pain, which can be exacerbated by prolonged use of the affected tendon. We report a case of calcific tendinosis in the posterior tibialis tendon at the navicular insertion.

Pathological studies of cheek teeth apical infections in the horse: 5. Aetiopathological findings in 57 apically infected maxillary cheek teeth and histological and ultrastructural findings.

Examination of 57 apically infected maxillary cheek teeth (CT) showed one or more viable pulps and minimal apical calcified tissue changes present in recently infected CT. With chronic infections, pulps were necrotic or absent, pulp horns were filled with food if occlusal pulpar exposure was present, and gross caries of dentine was occasionally present. With chronic infections, the apical changes varied from gross destructive changes in some teeth, to extensive proliferative calcified apical changes in others.

Pathological studies of cheek teeth apical infections in the horse: 4. Aetiopathological findings in 41 apically infected mandibular cheek teeth.

Examination of 41 extracted, apically infected mandibular cheek teeth (CT) without obvious causes of infection included radiography, computerised axial tomography and decalcified and undecalcified histology. In CT with recent infections, some pulps remained viable, with proliferative soft and calcified tissue changes confined to the apex. With more advanced CT infections, occlusal pulpar exposure was sometimes present (in 34% of the 41 CT), some infected pulp chambers were filled with necrotic pulp or food, and extensive destructive or proliferative changes were present in the calcified apical tissues.

Pathological studies of cheek teeth apical infections in the horse: 1. Normal endodontic anatomy and dentinal structure of equine cheek teeth.

Morphological examinations were performed on 100 normal equine cheek teeth (CT) of 1-12 years dental age (i.e. time since eruption), using gross examination, dissection microscopy, computerised axial tomography, and decalcified and undecalcified histology.

Pathological investigation of caries and occlusal pulpar exposure in donkey cheek teeth using computerised axial tomography with histological and ultrastructural examinations.

Post-mortem examination of 16 donkey cheek teeth (CT) with caries (both peripheral and infundibular) and pulpar exposure were performed using computerised axial tomography (CAT), histology and scanning electron microscopy. CAT imaging was found to be useful to assess the presence and extent of caries and pulp exposure in individual donkey CT. Histology identified the loss of occlusal secondary dentine, and showed pulp necrosis in teeth with pulpar exposure.

Acute inhibition of the betaine transporter by ATP and adenosine in renal MDCK cells.

Extracellular ATP interacts with purinergic P2 receptors to regulate a range of physiological responses, including downregulation of transport activity in the nephron. ATP is released from cells by mechanical stimuli such as cell volume changes, and autocrine signaling by extracellular ATP could occur in renal medullary cells during diuresis. This was tested in Madin-Darby canine kidney (MDCK) cells, a model used frequently to study P1 and P2 receptor activity.

Donkey dental anatomy. Part 1: Gross and computed axial tomography examinations.

Post-mortem examination of 19 donkey skulls showed that donkeys have a greater degree of anisognathia (27% width difference between upper and lower jaws) compared to horses (23%). Teeth (n=108) were collected from 14 skulls and examined grossly and by computed axial tomography (CAT). A greater degree of peripheral enamel infolding was found in mandibular cheek teeth (CT) compared to maxillary CT (P<0.

Donkey dental anatomy. Part 2: Histological and scanning electron microscopic examinations.

Ten normal cheek teeth (CT) were extracted at post mortem from donkeys that died or were euthanased for humane reasons. Decalcified histology was performed on three sections (sub-occlusal, mid-tooth and pre-apical) of each tooth, and undecalcified histology undertaken on sub-occlusal sections of the same teeth. The normal histological anatomy of primary, regular and irregular secondary dentine was found to be similar to that of the horse, with no tertiary dentine present.

Nitric oxide production by mouse renal tubules can be increased by a sodium-dependent mechanism.

Renal tubules process large amounts of NaCl that other investigators indicate increases tubular generation of nitric oxide. We questioned whether medullary or superficial cortical tubules would have the greater increase in nitric oxide concentration, [NO], when stressed by sodium and if the sodium/calcium exchanger was involved. Sodium stress in proximal tubules is due to the large amount of sodium absorbed and medullary tubules exist in a hypertonic sodium environment.

Inhibition of the renal betaine transporter by calcium ions.

Chronic upregulation of the renal betaine/GABA transporter (BGT1) by hypertonic stress has been well documented, but it is not known whether BGT1 can be regulated acutely after insertion in the basolateral plasma membrane. Related transporters, such as the rat brain GABA transporter, can be rapidly removed from the plasma membrane through activation of G protein-coupled receptors. The goal of the present study was to determine whether acute changes in extracellular and/or intracellular Ca(2+) will regulate BGT1 transport activity at the plasma membrane level in Madin-Darby canine kidney cells subjected to 24-h hypertonic stress.

Membrane insertion of betaine/GABA transporter during hypertonic stress correlates with nuclear accumulation of TonEBP.

MDCK cells stably transfected with betaine/GABA transporter tagged with EGFP (EGFP-BGT) were used to study plasma membrane insertion of EGFP-BGT. Adaptive response to hypertonicity requires nuclear migration of TonEBP. Confocal microscopy showed that after 6 h hypertonicity, the nuclear/cytoplasmic ratio of TonEBP fluorescence was increased to 2.

Hypertonic upregulation of betaine transport in renal cells is blocked by a proteasome inhibitor.

The renal betaine transporter (BGT1) protects cells in the hypertonic medulla by mediating uptake and accumulation of the osmolyte betaine. Transcription plays an essential role in upregulating BGT1 transport in MDCK cells subjected to hypertonic stress. During hypertonic stress, the abundance of the transcription factor TonEBP increases and it shifts from the cytoplasm to the nucleus where it activates transcription of the BGT1 gene.

Osmotic regulation of renal betaine transport: transcription and beyond.

Cells in the kidney inner medulla are routinely exposed to high extracellular osmolarity during normal operation of the urinary concentrating mechanism. One adaptation critical for survival in this environment is the intracellular accumulation of organic osmolytes to balance the osmotic stress. Betaine is an important osmolyte that is accumulated via the betaine/gamma-aminobutyric acid transporter (BGT1) in the basolateral plasma membrane of medullary epithelial cells.

Use of a topical disinfectant as part of a hoof care programme for horses with diseases of the hoof capsule.

Twenty-three horses with persistent hoof horn defects were treated topically with a hoof disinfectant as part of a hoof care programme for a year. The active ingredients of the disinfectant were a poloaximer-iodine complex, ethylenediamine dihydriodide, isopropyl alcohol and propylene glycol. Hoof trimmings were taken at the start of the study and every six weeks, and examined by scanning and transmission electron microscopy.