Disease relevance of PBEF1

• Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis [1].
• In this study, we examined whether visfatin plasma concentrations (using enzyme immunosorbent assay) and mRNA expression (using RT-PCR) in visceral and subcutaneous fat correlates with anthropometric and metabolic parameters in 189 subjects with a wide range of obesity, body fat distribution, insulin sensitivity, and glucose tolerance [2].
• OBJECTIVES: In this study we investigated whether plasma visfatin level is altered in patients with type 2 diabetes mellitus (T2DM) [3].
• Prior genomic and genetic studies identified pre-B-cell colony-enhancing factor (PBEF) as a novel candidate gene and biomarker in acute lung injury (ALI) [4].
• Although these data confirm an involvement of PBEF in disease progression, the consequence of its action remains to be determined [5].

High impact information on PBEF1

• Inhibition of apoptosis by PBEF is associated with reduced activity of caspases-8 and -3, but not caspase-9 [1].
• We show here that PBEF is also upregulated in neutrophils by IL-1beta and functions as a novel inhibitor of apoptosis in response to a variety of inflammatory stimuli [1].
• Pre-B cell colony-enhancing factor (PBEF) is a highly conserved 52-kDa protein, originally identified as a growth factor for early stage B cells [1].
• Expression occurs at higher levels than those seen in experimental inflammation, and a PBEF antisense oligonucleotide significantly restores the normal kinetics of apoptosis in septic polymorphonuclear neutrophils [1].
• A novel gene coding for the pre-B-cell colony-enhancing factor (PBEF) has been isolated from a human peripheral blood lymphocyte cDNA library [6].

Chemical compound and disease context of PBEF1

• Desferoxamine and Cobaltous chloride, two hypoxia mimetic compounds, also increased visfatin mRNA levels [7].

Biological context of PBEF1

• Genetic variation in the visfatin gene (PBEF1) and its relation to glucose metabolism and fat-depot-specific messenger ribonucleic acid expression in humans [8].
• Visfatin gene expression was not different between visceral and subcutaneous adipose tissue in the entire study group nor in selected subgroups [2].
• As increased vascular permeability is a cardinal feature of ALI, we assessed the role of PBEF in in vitro vascular barrier regulation using confluent human pulmonary artery endothelial cell (HPAEC) monolayers [4].
• Reductions in PBEF protein expression (>70%) by siRNA significantly attenuated EC barrier dysfunction induced by the potent edemagenic agent, thrombin, reflected by reductions in transendothelial electric resistance (TER, approximately 60% reduction) [4].
• Furthermore, PBEF siRNA blunted thrombin-mediated increases in Ca(2+) entry, polymerized actin formation, and myosin light chain phosphorylation, events critical to the thrombin-mediated permeability response [4].

Anatomical context of PBEF1

• PBEF itself had no activity but synergized the pre-B-cell colony formation activity of stem cell factor and interleukin 7 [6].
• The PBEF gene is mainly transcribed in human bone marrow, liver tissue, and muscle [6].
• Recently, visfatin was identified as an adipokine, which is predominantly secreted from visceral adipose tissue both in humans and mice [2].
• In addition, we did not find differences in visfatin mRNA expression between visceral and subcutaneous adipose tissue in humans [2].
• We found no significant correlation between visfatin plasma concentrations and parameters of insulin sensitivity, including fasting insulin, fasting plasma glucose concentrations, and the glucose infusion rate during the steady state of an euglycemic-hyperinsulinemic clamp independent of percent body fat [2].

Associations of PBEF1 with chemical compounds

• STUDY DESIGN: Pre-B-cell colony-enhancing factor secretion was studied from amniotic epithelial-like WISH cells and primary amniotic epithelial cells that were seeded on squares of immobilon-P membrane and stimulated with lipopolysaccharide or tumor necrosis factor-alpha, respectively [9].
• Apoptosis was induced in primary amniotic epithelial cells and fibroblasts by actinomycin D (1 microg/mL); the antiapoptotic effects of pre-B-cell colony-enhancing factor on early apoptosis were measured by the annexin V assay, and the late effects were determined by measurement of nuclear matrix protein in the media [9].
• A chemotaxic effect of pre-B-cell colony-enhancing factor on human neutrophils was compared with the chemoattractants interleukin-8 and N-Formyl-Met-Leu-Phe methyl ester in a rapid fluorescence-based neutrophil migration assay [9].
• We demonstrate that infected RBCs have readily detectable nicotinamide phosphoribosyltransferase (NPRT), the first enzyme in the NAD biosynthetic pathway that uses nicotinamide, and abundant nicotinamide deamidase, the enzyme that converts nicotinamide to nicotinic acid, thereby indicating that infected RBCs can make NAD from nicotinamide [10].
• Effect of Rosiglitazone on Visfatin and Retinol-Binding Protein-4 Plasma Concentrations in HIV-Positive Patients [11].
• Under physiologic conditions, visfatin does not appear to control glucose metabolism but may play a regulatory role in lipid metabolism [12].
• There was a positive correlation between visfatin and fasting insulin (r = 0.38, p = 0.007) and insulin at 120 min of the OGTT (r = 0.39, p = 0.006) [13].

Regulatory relationships of PBEF1

• OBJECTIVE: Our purpose was to determine whether pre-B-cell colony-enhancing factor (PBEF) is expressed in the human fetal membranes during normal gestation and parturition in the absence of infection and to show its effects on the expression of interleukin (IL)-6 and IL-8 [14].
• Common Polymorphisms in the Promoter of the Visfatin Gene (PBEF1) Influence Plasma Insulin Levels in a French-Canadian Population [15].

Other interactions of PBEF1

• DESIGN AND PATIENTS: Plasma visfatin as well as adiponectin and resistin concentrations were measured through ELISA in type 2 diabetic and nondiabetic subjects [3].
• Finally, PBEF siRNA also significantly inhibited thrombin-stimulated increase of IL-8 secretion in HPAEC, a chemokine known to induce actin fiber formation and intercellular gap formation of endothelial cells [4].
• Pre-B-cell colony-enhancing factor is a secreted cytokine-like protein from the human amniotic epithelium [9].
• Glucose-induced elevation of visfatin was prevented by co-infusion of insulin or somatostatin (p<0.05) [16].
• Fasting visfatin, RBP-4, leptin, and adiponectin plasma concentrations were analyzed by immunoassays [11].

Analytical, diagnostic and therapeutic context of PBEF1

• In conclusion, visfatin plasma concentrations and visceral visfatin mRNA expression correlated with measures of obesity but not with visceral fat mass or waist-to-hip ratio [2].
• We found a significant correlation between visceral visfatin gene expression and BMI (r(2) = 0.06, P = 0.001) and percent body fat (measured using dual-energy X-ray absorptiometry) (r(2) = 0.044, P = 0.004), whereas no significant association between BMI or percent body fat and subcutaneous visfatin mRNA expression existed (both P >0.5) [2].
• Medium and cell lysates that were obtained from WISH cells that were treated with lipopolysaccharide alone or together with a pre-B-cell colony-enhancing factor antisense oligonucleotide to block pre-B-cell colony-enhancing factor translation were also analyzed for secreted pre-B-cell colony-enhancing factor by Western blotting and densitometry [9].
• The pre-B-cell colony-enhancing factor protein was detected both intracellularly and after secretion, as bound to the membrane, by immunostaining and densitometry [9].
• Xenotransplantation of human SMCs into immunodeficient mice revealed an increased capacity for PBEF-overexpressing SMCs to mature and intimately invest nascent endothelial channels [17].

References