Disease relevance of GC

• Using fluorescent microscopy and temperature-shift techniques, we found that T-47D breast cancer cells rapidly internalize DBP via endocytosis, which is blunted by receptor-associated protein, a specific inhibitor of megalin-mediated endocytosis [1].
• In an earlier paper, positive but nonsignificant lod scores were found in pair-wise linkage tests between multiple endocrine neoplasia type 2A (MEN-2A) and both the haptoglobin (HP) locus on chromosome 16 and group-specific component (GC) locus on chromosome 4 [2].
• Full-length and truncated versions of DBP (Gc-2 allele) were expressed in Escherichia coli using a glutathione S-transferase fusion protein expression system [3].
• Therefore, allelic variants of the DBP gene confer susceptibility to Graves' disease but not to Hashimoto's thyroiditis in our population [4].
• The purpose of this investigation is to determine whether novel single nucleotide polymorphisms (SNPs) within the transcriptional regulatory regions of the VDR and DBP are associated with prostate cancer risk [5].

Psychiatry related information on GC

• The proportion of alcoholic patients considered hypertensive on the basis of 24-hour BP criteria (daytime SBP >/=135 mm Hg or daytime DBP >/=85 mm Hg) fell from 42% during alcohol drinking to 12% after 1 month of complete abstinence [6].
• In the present study we aimed at determining for the first time whether metabolic changes would also occur in vascular dementia (VD) patients in the supraoptic (SON), infundibular (INF), tuberomamillary (TMN), medial mamillary nuclei, vertical limb of the diagonal band of Broca (VDB), and nucleus basalis of Meynert [7].
• The association between DBP and SBP by tertiles, and spatial functions (Block Design and Benton Visual Retention test) remained after controlling for education, marital status, smoking, alcohol and physical activity, and intermediates such as arteriosclerotic manifestations (block design, beta = 0.17; = 0.029) in multiple regression models [8].
• The slopes of the relationship between MSNA and DBP were more negative (steeper) in the panic disorder group compared with the control subjects (-5.97 +/- 0.45 versus -3.06 +/- 0.43 bursts/100 heart beats per mmHg, P < 0.001) [9].
• Among pain-free normotensives, elevated resting systolic (SBP) and diastolic (DBP) blood pressure were associated with significantly higher ISC pain thresholds (P values <0.05) [10].

High impact information on GC

• This Rac/PAK/GC/cGMP pathway is involved in platelet-derived growth factor-induced fibroblast cell migration and lamellipodium formation [11].
• Vitamin D binding protein (Gc-globulin) [12].
• Now we summarize the role of basic region/leucine zipper protein family members and particularly the albumin D site-binding protein (DBP) and the CAAT/enhancer-binding proteins (C/EBPs) for their importance in liver-specific gene expression and their role in liver function and development [13].
• Specifically, regulatory networks and molecular interactions were examined in detail, and the experimental findings summarized in this review point to pivotal roles of DBP and C/EBPs in cell cycle control, carcinogenesis, circadian gene regulation, liver regeneration, apoptosis, and liver-specific gene regulation [13].
• Gc globulin and deoxyribonuclease I, proteins that sequester monomeric actin but do not sever actin filaments, were less efficient than gelsolin in diminishing sputum viscosity [14].

Chemical compound and disease context of GC

• In summary, these studies demonstrate transcriptional regulation of the exon 1c VDR promoter in breast cancer cells, and identify three distinct GC-rich, Sp1 consensus sites that differentially confer responsiveness to estrogen, resveratrol and 1,25(OH)(2)D(3) [15].
• Fasting plasma concentrations of total homocysteine, methionine, cysteine, and cystathionine were determined by gas chromatography-mass spectrometry (GC-MS) in 131 ESRD patients receiving daily oral folate (160-320 microg) and vitamin B6 (10-20 mg) supplements [16].
• OBJECTIVE: To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials [17].
• We measured the free concentration of 1,25-dihydroxyvitamin D (1,25[OH]2D) using centrifugal ultrafiltration, and the level of vitamin D-binding protein (DBP) in 24 normal subjects, 17 pregnant subjects, and 25 alcoholic subjects with liver disease [18].
• We have recently reported the association of the DBP genotype with type 2 diabetes mellitus in Japan. The aim of this study was to investigate whether genetic variations of DBP have any influence on glucose metabolism without secondary effects of hyperglycemia or diabetes mellitus using 82 Japanese with normal glucose tolerance [19].

Biological context of GC

• The GC gene, and the tandemly linked ALB and AFP genes, have been previously localized to human chromosome 4q11-13 [20].
• It appears that GC is very close (and may be the gene proximal) to the centromere [20].
• Statistically significant linkage disequilibrium between the AluVpA and the GC iso-electric focusing (IEF) phenotypes was found in a sample of 188 unrelated individuals and delta values were calculated from the observed haplotype distribution [21].
• The GC polymorphism revealed by Southern blot analysis of StyI-digests provides an informative DNA marker system for chromosome 4q11-q13 [22].
• In a single case, the observed result of the StyI-digest differed from the result expected after IEF classification: homozygous GC 1F-1F by IEF and heterozygous by StyI RFLP analysis [22].

Anatomical context of GC

• Radioiodinated DBP (125I-DBP) was used to follow the uptake of the protein by Raji cells, a human pre-B-lymphoma cell line [23].
• In this work, we demonstrate that normal and malignant human B-lymphocytes specifically bind and internalize DBP [23].
• Accordingly, most DBP molecules accumulated in endosomes should be degraded in lysosomes, instead of being recycled back to the surface, as in the case of AFP [23].
• Their binding affinity was examined with calf thymus cytosolic vitamin D receptor (VDR) and rat plasma vitamin D-binding protein (DBP) [24].
• The human serum vitamin D-binding protein (DBP) has many physiologically important functions, ranging from transporting vitamin D3 metabolites, binding and sequestering globular actin and binding fatty acids to functioning in the immune system [25].

Associations of GC with chemical compounds

• Vitamin D-binding protein (DBP), a member of a multigene family including alpha-fetoprotein (AFP) and albumin, is a serum glycoprotein that reversibly binds and transports vitamin D and its metabolites to target cells [23].
• Most cell lines exhibited positive staining for alpha 2-macroglobulin (alpha 2M) and also, to a lesser extent, for serum Vitamin D3 binding protein (DBP) [26].
• We recently observed that mammary cells can metabolize 25(OH)D3 to 1,25-dihydroxycholecalciferol [1,25(OH)(2)D3], the vitamin D receptor (VDR) ligand, and the objective of our study was to elucidate the mechanisms by which the 25(OH)D3-DBP complex is internalized by mammary cells prior to metabolism [1].
• The major circulating form of vitamin D is 25-hydroxycholecalciferol [25(OH)D3], which is delivered to target tissues in complex with the serum vitamin D binding protein (DBP) [1].
• Dibutyryl cAMP-differentiated HL-60 cells were utilized to test purified natural DBP and recombinant expressed DBP (reDBP) for their ability to enhance chemotaxis and intracellular Ca(2+) flux to C5a [3].

Physical interactions of GC

• Platelet-derived thrombospondin-1 is necessary for the vitamin D-binding protein (Gc-globulin) to function as a chemotactic cofactor for C5a [27].
• BACKGROUND: The vitamin D receptor (VDR) and binding protein (DBP) mediate the cellular transport, activity, and anti-tumor action of 1,25-dihydroxyvitamin D3 [1,25-(OH)(2)D3] [5].
• DBP binds to CD44 on the cell surface as evidenced by coimmunoprecipitation, confocal microscopy, and cell binding studies [28].
• Genetic polymorphism was detected in the red deer (Cervus elaphus L.), plasma proteins, plasminogen (PLG) and vitamin D binding protein (GC) using antiserum to human proteins [29].
• The RNase-gold complex does not bind to the FC but to the DFC and the GC, suggesting that rDNA transcription does not occur in the FC although both fluorescence in situ hybridization (FISH) and electron microscopic in situ hybridization reveal that the rDNA is specifically localized in the FCs [30].

Regulatory relationships of GC

• DBP induced both proliferation and migration of VSMC in vitro in association with increased phosphorylation of ERK 1/2 [31].

Other interactions of GC

• The results suggest that, unlike the corresponding sequences in the ALB and AFP genes, chromosomal sequences encoding the first domain and the leader sequence of the GC gene have specifically been conserved throughout vertebrate evolution [32].
• Serum protein polymorphisms (GC, TF, and PI subtypes) in the Basque population of Alava [33].
• The levels of certain other proteins, like haptoglobin, fibrinogen, complement component 3, and Gc-globulin, were altered in the disease group as well, however, the changes did not reach a statistical significance [34].
• The more extensive interactions of DBP give an affinity for actin some 3 orders of magnitude higher than that for profilin [35].
• These results provide clear evidence that CD44 and annexin A2 mediate the C5a chemotactic cofactor function of DBP [28].

Analytical, diagnostic and therapeutic context of GC

• We have tested 140 individual genomic DNA samples for the HaeIII site and 148 samples for the StyI site by restriction fragment length polymorphism (RFLP) analysis with a DBP-specific direct genomic DNA probe, and have compared these findings with the GC phenotype classification, by isoelectric focusing (IEF) of the corresponding plasma [22].
• GC was considered to be the most suitable marker for routine screening because of its high stability and Dp, and the sensitivity of the immunoblotting detection method [36].
• Immunoprecipitation of detergent-soluble lysates with the polyclonal anti-DBP showed only the 56-Kd form by Western blotting [37].
• Immunofluorescence studies of normal untreated neutrophils showed the presence of DBP on the cell surface [37].
• Quantitation of the immunoreactive bands by video densitometry indicated that normal human neutrophils contain 1.5 +/- 0.8 ng DBP/10(6) cells (n = 9) [37].

References