Disease relevance of Cfd

• We showed previously a cause and effect relationship between increased activity of an endogenous vascular elastase (EVE) and experimentally induced pulmonary hypertension in rats [1].
• Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor [2].
• It has been suggested that this reduction in adipsin is causative to obesity development [3].
• Ultrastructural observations in lung tissue implicated an endogenous vascular elastase (EVE), in the pathobiology of pulmonary vascular disease [4].

High impact information on Cfd

• Immunogold labeling with an antibody to an adipsin peptide sequence localized EVE to PA smooth muscle cells [1].
• This is the first isolation of EVE; it appears to be a novel enzyme related to the serine proteinase adipsin originally found in adipose tissue [1].
• The endogenous vascular elastase that governs development and progression of monocrotaline-induced pulmonary hypertension in rats is a novel enzyme related to the serine proteinase adipsin [1].
• The PCR product was used to screen a cDNA library and sequences obtained encoded rat adipsin [1].
• The enzyme was purified using an antibody that recognizes NH2-terminal sequences of serine proteinases and the eluate was further purified using an antibody raised against recombinant adipsin [1].

Biological context of Cfd

• METHODS: Df-protease was incubated with human serum C3 or C5 in a purified system, and the anaphylatoxin activity produced was assayed by measuring enhancement of vascular permeability and release of histamine from mast cells triggered by C3a and by assessing chemotaxis of polymorphonuclear cells caused by C5a [5].
• We also determined levels of mRNA encoding adipsin, a fat cell-derived protein possibly associated with lipid metabolism [6].
• Regulation of gene expression by insulin in adipose cells: opposite effects on adipsin and glycerophosphate dehydrogenase genes [7].
• Induction of EVE can release basic fibroblast growth factor from the extracellular matrix in an active form stimulating smooth muscle cell proliferation [4].

Anatomical context of Cfd

• Additionally, the aberrant expression of adipsin, and its presence in feces may serve as a noninvasive biomarker of gastrointestinal toxicity associated with perturbed Notch signaling [2].
• Microarray analysis of ileum from FGSI-treated rats revealed differential expression responses in a number of genes indicative of Notch signaling perturbation, including the serine protease adipsin [2].
• When compared with controls or nonresponding tumors, the expression of adipocyte-related genes such as adipocyte P2 (aP2), adipsin, peroxisome proliferator-activated receptor gamma (PPARgamma), and lipoprotein lipase was elevated in LGD1069-responding tumors [8].
• 5. Expression of adipsin in rat skeletal muscles coupled to very low levels of beta 3-AR mRNA indicates that the observed beta 3-AR may be due to the presence of intrinsic fat. beta 3-AR mRNA was virtually undetectable in heart, lung and liver [9].
• Pylorus and colon mucosa showed moderate levels of beta 3-AR mRNA with lower levels of adipsin [9].

Associations of Cfd with chemical compounds

• An appreciable amount of Df-protease was recovered in the house dust extract, and the house dust protease caused C5a release from C5 [5].
• OBJECTIVE: The purpose of this study was to determine whether Df-protease could enzymatically generate anaphylatoxins from complement components C3 and C5 [5].
• RESULTS: Df-protease showed strong activation of C3 and C5, producing C3a and C5a by proteolytic cleavage of the complements [5].
• We previously showed that the 30 kd protease from Dermatophagoides farinae (Df-protease) could activate the bradykinin-generating cascade and exacerbate inflammatory reactions [5].
• Adenosine (Adn; 10(-4) M), an endothelium-independent agent, produced similar dilation (127% of control) but did not alter endothelial cell calcium [10].

Regulatory relationships of Cfd

• The metallothionein-1 gene was expressed in the adipocytes prior to the adipsin and lipoprotein lipase genes, suggesting that it is an early marker of adipocyte differentiation [11].

Other interactions of Cfd

• Lipoprotein lipase, adipsin, and adipocyte P2 mRNAs were found in substantial levels in both the adipocytes and stromal-vascular cells, but with higher levels present in the adipocytes [12].
• There were only minimal, or no, effects on acrp30/adiponectin, resistin, adipsin, or stearoyl-CoA desaturase 1 [13].
• Fatty acid synthase and adipsin mRNA levels in obese and lean JCR:LA-cp rats: effect of diet [6].
• The absence of markers for adipsin or hormone-sensitive lipase in endothelial cells excluded the presence of beta(3)-AR from adipocytes [14].

Analytical, diagnostic and therapeutic context of Cfd

• The PCR product hybridized to a 1.2-kb mRNA and the intensity of hybridization was threefold increased in RNA from rat hypertensive PA at a timepoint when EVE activity was increased [1].
• We were able to show that FGSI-treated rats had elevated levels of adipsin protein in gastrointestinal contents and feces, and by immunohistochemistry demonstrated that adipsin containing ileum crypt cells were increased in FGSI-treated rats [2].
• We investigated expression of the adipose-specific serine protease adipsin in genetically obese Zucker rats and whether adrenalectomy modifies expression [15].
• In both experiments, serum adipsin protein was determined by Western blot analysis and plasma insulin by radioimmunoassay [15].
• Adipsin mRNA levels were determined by slot blot and Northern blot analysis of total RNA samples extracted from epididymal adipose tissue and isolated retroperitoneal adipocytes of obese (fa/fa) and homozygous lean (Fa/Fa) Zucker rats [15].

References