Disease relevance of Slc6a12

• Western blotting showed a significant decrease in the VGAT immunoreactive protein levels in the ipsilateral cortex of rats subjected to focal ischemia and 24 h reperfusion [1].
• Whereas in both H4IIE rat hepatoma cells and primary hepatocytes TAUT mRNA levels were strongly dependent upon ambient osmolarity, mRNAs for other osmolyte transporters, i.e. the betaine transporter BGT-1 and the Na+/myo-inositol transporter SMIT, were not detectable [2].
• On the other hand, excessive or prolonged BGT-1 expression might be a factor contributing to astrocytic swelling after brain injury [3].
• Amacrine cell somata characterized by weak VGAT immunoreactivity in the cytoplasm were located in the ganglion cell layer and proximal inner nuclear layer (INL) adjacent to the IPL [4].
• However, experimental hyperglycemia did not significantly affect the expression of mRNA for BGT-1 isoform by osteoblasts [5].

High impact information on Slc6a12

• Here, we propose that there is a functional and structural coupling between the synthesis of gamma-aminobutyric acid (GABA) by membrane-associated GAD and its packaging into synaptic vesicles (SVs) by vesicular GABA transporter (VGAT) [6].
• Betaine uptake increased twofold because of osmosensitive induction of BGT1 expression [7].
• In contrast, hippocampal mossy fiber boutons, which although glutamatergic are known to contain GABA, lack VGAT immunoreactivity [8].
• The vesicular GABA transporter, VGAT, localizes to synaptic vesicles in sets of glycinergic as well as GABAergic neurons [8].
• Although the great majority of nerve terminals containing GABA or glycine are immunopositive for VGAT, subpopulations of nerve endings rich in GABA or glycine appear to lack the protein [8].

Biological context of Slc6a12

• These findings support the view that the effect of intracellular ionic strength on the expression of bgt1, smit, ar and osp94 is modulated by additional factors such as cell volume, and that its effect on the pathways regulating hsp70 and inos is even more complex [9].
• The gamma-aminobutyric acid (GABA) transporters GAT-1, GAT-2, GAT-3, and BGT-1 have been cloned and identified according to their differential amino acid sequences and pharmacologic properties [3].
• Changes in GABA transporters in the rat hippocampus after kainate-induced neuronal injury: decrease in GAT-1 and GAT-3 but upregulation of betaine/GABA transporter BGT-1 [3].
• DIZ caused increase in the quantity of VGAT mRNAs and proteins, and down regulation of GABA transporters GAT-1 and GAT-3 mRNAs and proteins after the PTX re-kindling [10].

Anatomical context of Slc6a12

• From P10 onward, labeled puncta were both scattered in the neuropil and in apposition to unstained cellular profiles; VGAT was also expressed in few GABAergic cell bodies [11].
• Surprisingly, in the mossy fiber synaptosomes of seizing rats, the levels of VGAT mRNA were significantly higher than in controls [12].
• To address this, using RT-PCR we looked for the presence and regulation of expression of the vesicular GABA transporter (VGAT) mRNA in the dentate gyrus and in mossy fiber synaptosomes of control and kindled rats [12].
• Ethanol induces GAD67 and VGAT in slice cultures of newborn rat cerebral cortex [13].
• Moreover, dual-phenotype synaptic terminals contact GnRH neurons, and at the time of the surge, VGAT-containing vesicles decrease and VGLUT2-containing vesicles increase in these terminals [14].

Associations of Slc6a12 with chemical compounds

• This was investigated here by studying the effect of aniso-osmotic exposure of rat liver sinusoidal endothelial cells (SEC) on osmolyte transport and the messenger RNA (mRNA) levels for the transport systems for betaine (BGT1), taurine (TAUT), and myo-inositol (SMIT) [15].
• VGLUT3-immunoreactive axon terminals were immunopositive for either vesicular GABA transporter (VGAT) or serotonin [16].
• Intraperitoneal administration of NaCl rapidly increased the signal in the MTAL, and furosemide prevented the increase in BGT-1 mRNA by NaCl loading [17].
• In contrast, increased BGT-1 immunoreactivity was observed in astrocytes after kainate injection [3].
• RESULTS: While GAT-1 was upregulated, VGAT expression declined in cortical and limbic brain regions, whereby haloperidol showed a greater effect than clozapine [18].

Other interactions of Slc6a12

• Following transient focal ischemia, mRNA expression of the vesicular GABA transporter (VGAT) decreased significantly by 3 h of reperfusion and remained at a significantly lower level than sham until at least 72 h of reperfusion [1].
• We exposed organotypic slice cultures of newborn rat cerebral cortex to ethanol (100 mM) for 4 days and observed a significant induction of the enzyme producing GABA (GAD67, +21%) and the vesicular transporter VGAT (+112%), whereas the expression of the transmembrane transporters did not differ from control conditions [13].

Analytical, diagnostic and therapeutic context of Slc6a12

• Immunohistochemistry demonstrated many VGAT immunopositive puncta in the contralateral cortex, which were significantly decreased in the ipsilateral cortex at 24 h reperfusion [1].
• Light and electron microscopic immunocytochemical techniques and Western blotting were used to investigate the postnatal development of the vesicular GABA transporter (VGAT) in the rat somatic sensory cortex [11].
• In situ hybridization revealed that BGT-1 mRNA is predominantly present in the outer medulla and papilla [17].
• Preembedding immunoelectron microscopy of mouse and rat retinae showed that VGAT immunoreactivity was localized to horizontal cell processes and their terminals [4].
• The localization of VGAT immunoreactivity to mouse and rat retina was evaluated with light and electron microscopy by using well-characterized VGAT antibodies [4].

References