Disease relevance of SLC2A1

• Hypoxia (0.5% O2, 5% CO2, and 94.5% N2) stimulated GLUT1 mRNA expression in BRECs in a time-dependent manner with an 8.9 +/- 1.5-fold (P < 0.01) increase observed after 12 h [1].
• Transfection of C6 glioma cells with pGL2 (containing nucleotides 2,100-2,300 of the bovine GLUT1 3'-UTR inserted at the Pfl MI site within the luciferase 3'-UTR) results in a fivefold increase in luciferase gene expression [2].
• The absence of neuroglucopenia symptoms in chronic hypoglycemia may be due to up-regulation of the blood-brain barrier glucose transporter type 1 (GLUT1) [3].

High impact information on SLC2A1

• The transport of glucose across the mammalian blood-brain barrier is mediated by the GLUT1 glucose transporter, which is concentrated in the endothelial cells of the cerebral microvessels [4].
• Several studies supported an asymmetric distribution of GLUT1 protein between the luminal and abluminal membranes (1:4) with a significant proportion of intracellular transporters [4].
• Western blot analysis with antibodies raised against either the intracellular loop of GLUT1 or the purified erythrocyte protein exhibited luminal:abluminal ratios of 1:1 [4].
• These data suggest that hypoxia in BRECs upregulates glucose transport activity through an increase of GLUT1 expression that is partially mediated by adenosine, A2R, and the cAMP-PKA pathway [1].
• The adenosine A2a receptor antagonist 8-(3-chlorostyryl)caffeine (CSC) (Kd = 100 nmol/l for A2R) inhibited hypoxia-stimulated GLUT1 mRNA expression by 40 +/- 8% at 100 nmo/l. Hypoxia upregulated GLUT1 protein expression by 3.0 +/- 0.3-fold after 12 h (P < 0.01), but this response was attenuated by CSC (P < 0.05) [1].

Chemical compound and disease context of SLC2A1

• Hypoxia upregulates glucose transport activity through an adenosine-mediated increase of GLUT1 expression in retinal capillary endothelial cells [1].

Biological context of SLC2A1

• An impaired expression of Glut leads to an increase in apoptosis at the blastocyst stage and involves Bax [5].
• Glucose deprivation causes posttranscriptional enhancement of brain capillary endothelial glucose transporter gene expression via GLUT1 mRNA stabilization [3].
• Taken together, these findings show that hyperglycaemia increases the production rate of 12-HETE, which in turn mediates the down-regulation of GLUT-1 expression and the glucose-transport system in vascular endothelial and smooth-muscle cells [6].
• Deletion of nucleotides 2,181-2,190 of the bovine GLUT1 3'-UTR, i.e., the putative binding site of the 80-kDa protein, completely eliminated the enhancement of luciferase activity in the transfected cells [2].
• These putative cis/trans interactions were examined in the present studies with RNase T1 protection assays using 32P-labeled GLUT1 3'-UTR prepared from transcription plasmids and cytosolic proteins from C6 rat glioma cells [7].

Anatomical context of SLC2A1

• The results show that bovine chromaffin cells express both GLUT1 and GLUT3 [8].
• Northern blot analysis indicated that the amount of message for the GLUT-1/erythrocyte form of the glucose transporter was specifically increased by treatment with VPF (5-fold), TNF (25-fold), or to both cytokines together (35-fold) [9].
• High-glucose concentrations downregulate glucose transport activity and GLUT 1 content in retinal capillary pericytes but not in endothelial cells [10].
• Culture in high glucose decreased the apparent amount of immunoreactive pericyte plasma membrane GLUT1 in immunoblots (0.611 to 0.055 versus 1.0 relative density units), decreased the binding of 3H-cytochalasin B to pericyte plasma membranes, and decreased the mRNA level for GLUT1 in pericytes by 25% [10].
• So far, glucose transport in the central nervous system (CNS) has only been shown to be achieved by facilitative transporters, in particular by GLUT1 at the blood-brain barrier and in glial cells and by GLUT3 in a subset of neurons [11].

Associations of SLC2A1 with chemical compounds

• Distinct regulation of glucose transport and GLUT1/GLUT3 transporters by glucose deprivation and IGF-I in chromaffin cells [8].
• Both types of stimulus increased the GLUT1 protein content in a cycloheximide (CHX)-sensitive manner, and the glucose transport rate was elevated by 3- to 4-fold after 48 h under both experimental conditions [8].
• In this study we investigated the activity and concentration of GLUT1 in isolated luminal and abluminal membrane fractions of bovine brain endothelial cells [4].
• To determine whether the increase in the abundance of the GLUT1 mRNA induced by glucose deprivation was due to increased stability of this transcript, the GLUT1 mRNA half-life was measured in ECL cells incubated with actinomycin D [3].
• Although it had no effect on the expression of the GLUT1 in retinas and cultured retinal endothelial cells, captopril at a concentration of 2 mM significantly inhibited the high-glucose-induced increase in GLUT1-mediated glucose transport in cultured retinal endothelial cells by 67% +/- 10% [12].

Physical interactions of SLC2A1

• An enhanced glucose transport in response to IGF-I appears to be coupled to activation of IGF receptor type 1 and GLUT1 translocation [13].
• PURPOSE: To investigate effects of vascular endothelial growth factor (VEGF) on glucose transport and GLUT1 glucose transporter expression in primary bovine retinal endothelial cell (BREC) cultures [14].
• Using RNA mobility shift, UV cross-linking, and in vitro degradation assays, followed by mass-spectrometric analysis, we identified calreticulin as a specific destabilizing trans-acting factor that binds to a 10-nucleotide cis-acting element (CAE(2181-2190)) in the 3'-untranslated region of GLUT-1 mRNA [15].

Regulatory relationships of SLC2A1

• The deduced amino acid sequence was 64% and 92% identical with bovine GLUT1 (GLUT ubiquitously expressed in all tissues) and rat GLUT4, respectively [16].
• Epidermal growth factor (EGF) stimulated both GLUT1 mRNA expression and cell proliferation [17].

Other interactions of SLC2A1

• GLUT 1 mRNA quantity decreased whereas GLUT 2 increased with age [18].
• Dc II, Glut-1, and Glut-4 were more abundant in the TE than in ICM [19].
• As part of the validation of this technique, we determined that there was no nonspecific amplification of bovine GLUTs by rhodopsin primers, that there were no differences in amplification due to different regions of the Glut gene amplified, and that there were no secondary structure effects on amplification [18].
• CONCLUSIONS: The present study demonstrates VEGF-mediated enhancement of retinal endothelial cell glucose transport and suggests that this increase is due to PKC beta-mediated translocation of cytosolic GLUT1 to the plasma membrane surface [14].
• Notably, the currents were desensitized, reduced in a glucose concentration-dependent manner, and markedly inhibited by either a second application of glucose or the addition of glucose to the patch electrode filling solution; they were potentiated, however, by treatment with cytochalasin B, a GLUT1 to GLUT5 inhibitor [20].

Analytical, diagnostic and therapeutic context of SLC2A1

• In contrast, Western blot analysis using a rabbit polyclonal antibody raised against the C-terminal 20 amino acids of GLUT1 indicated a 1:5 luminal:abluminal distribution [4].
• The GLUT1 3'-UTR between nucleotides 2,100 and 2,300 was generated by polymerase chain reaction and subcloned at a unique Pfl/MI site within the 3'-UTR of a luciferase gene within the mammalian expression vector pGL2 [7].
• Polymerase chain reaction, nucleotide sequencing, and Southern blot analyses revealed that the retinal pigment epithelial cells express GLUT-1, -3, and -5 genes [21].
• We have investigated the expression of two glucose transporter isoforms, Glut1 and 4, in 14- and 16-day-old bovine blastocysts (d14, d16) using RT-PCR, competitive RT-PCR and in situ hybridization [22].
• Enhanced GLUT1 glucose transporter and cytoskeleton gene expression in cultured bovine brain capillary endothelial cells after treatment with phorbol esters and serum [23].

References