Disease relevance of Aoc3

• Cecal ligation and puncture (CLP)-induced sepsis in mice was associated with perturbations in vascular adhesion molecules [1].
• A soluble form of VAP-1 is found in serum, where concentrations are enhanced in diabetes and obesity [2].
• CONCLUSION/INTERPRETATION: Increased semicarbazide-sensitive amine oxidase-mediated deamination could be involved in the cascade of atherogenesis related to diabetic complications [3].
• AIMS/HYPOTHESIS: Semicarbazide-sensitive amine oxidase has been recognised to be a potential risk factor in vascular disorders associated with diabetic complications and to be related to mortality in patients suffering from heart disease [3].
• Therefore, we conducted a study to localize VAP-1 in normal mice and human lungs and in two distinct murine models of lung inflammation [4].

Psychiatry related information on Aoc3

• Increased SSAO-mediated deamination may contribute to protein deposition, the formation of plaques, and inflammation, and thus may be involved in the pathophysiology of chronic vascular and neurological disorders, such as diabetic complications, atherosclerosis, and Alzheimer's disease [5].

High impact information on Aoc3

• VAP-1 helps to elucidate the complex heterotypic cell interactions that direct tissue-selective lymphocyte migration in man [6].
• The expression pattern, molecular mass, functional properties, and an amino-terminal amino acid sequence define VAP-1 as an endothelial ligand for lymphocytes [6].
• While this may still be true for neutrophils, Th1 and Th2 cells use alpha(4)-integrin and VAP-1, respectively, to adhere within the liver sinusoids [7].
• We produced mice deficient in an endothelial cell-surface oxidase (amine oxidase, copper containing-3 [AOC3], also known as vascular adhesion protein-1 [VAP-1]) and found that this enzyme is needed for leukocyte extravasation in vivo [8].
• In contrast, Stat6 signaling only partially mediated antigen-induced eosinophilia with no role in vascular adhesion molecule 1 expression [9].

Chemical compound and disease context of Aoc3

• Involvement of semicarbazide-sensitive amine oxidase-mediated deamination in atherogenesis in KKAy diabetic mice fed with high cholesterol diet [3].
• Involvement of SSAO-mediated deamination in adipose glucose transport and weight gain in obese diabetic KKAy mice [10].
• Diminished lung injury with vascular adhesion molecule-1 blockade in choline-deficient ethionine diet-induced pancreatitis [11].

Biological context of Aoc3

• SSAO mRNAs are present in several tissues, but strikingly, the highest levels of gene expression are found in adipose tissue and aorta [12].
• Cloning of mVAP-1 provides a valuable tool for in vivo studies of the significance of VAP-1 for lymphocyte-endothelial cell interactions and of the possible relationship between leukocyte adhesion and amine oxidase activity [13].
• Because of its known stimulatory effect on glucose transport, its biochemical properties and its pattern of expression and regulation, SSAO could play an important role in the regulation of adipocyte homeostasis [12].
• Inhibition of semicarbazide-sensitive amine oxidase also reduced oxidative stress, as shown by a reduction of malondialdehyde excretion [3].
• VAP-1 protein glycosylation was measured [2].

Anatomical context of Aoc3

• Molecular cloning of a major mRNA species in murine 3T3 adipocyte lineage. differentiation-dependent expression, regulation, and identification as semicarbazide-sensitive amine oxidase [12].
• Moreover, the expression of SSAO transcripts and activity are clearly down-regulated in white adipose tissue from obese Zücker rats [12].
• Vascular adhesion protein-1 (VAP-1) is an endothelial cell adhesion molecule which mediates lymphocyte binding to endothelial cells [14].
• The present studies investigated the potential vascular adhesion ligand interactions that determine the in vivo recruitment of NK cells to pulmonary and hepatic parenchyma, and s.c. tumor after treatment of mice with biologic response modifiers [15].
• Normal mice and human lungs revealed VAP-1 expression in the endothelium of large and mid-sized pulmonary vessels but not in alveolar septae, airway epithelium or blood cells [4].

Associations of Aoc3 with chemical compounds

• RESULTS: Both MDL-72974A, a selective mechanism-based semicarbazide-sensitive amine oxidase inhibitor and aminoguanidine effectively inhibited aorta semicarbazide-sensitive amine oxidase activity, and caused a substantial increase in urinary methylamine, and a decrease in formaldehyde and methylgloxal levels [3].
• The release of soluble VAP-1 was enhanced by exposure of murine and human adipocytes to TNF-alpha and blocked by batimastat, a metalloprotease inhibitor [2].
• In the present study, we assessed the possibility of transcriptional regulation by analyzing SSAO activity and SSAO-mRNA levels in mice with alloxan-induced diabetes [16].
• Semicarbazide-sensitive amine oxidases (SSAO) are enzymes that are capable of deaminating primary amines to produce aldehyde, ammonia, and hydrogen peroxide [17].
• Vascular adhesion protein 1 (VAP-1) is an endothelial surface glycoprotein with two functions [18].

Regulatory relationships of Aoc3

• The release of soluble VAP-1/SSAO by 3T3-L1 adipocytes is stimulated by isoproterenol and low concentrations of TNFalpha [19].

Other interactions of Aoc3

• Interestingly, SSAO mRNA levels and enzyme activity drop in response to effectors of the cAMP pathway and to the cytokine tumor necrosis factor-alpha, indicating that two major signaling molecules of adipose tissue development and metabolism can control SSAO function [12].
• BACKGROUND: Plasma activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be significantly higher in diabetic patients compared to healthy controls [16].
• The infiltration of CD43+ leukocytes also coincided with the upregulation of vascular adhesion molecules, but CD43+ cells remained in the CNS after ICAM-1 and VCAM-1 had returned to control levels [20].
• The aim of this study was to examine how the murine liver and activation-regulated chemokine (mLARC/CCL20) contributes to lymphocyte recruitment in concert with vascular adhesion molecules in murine chronic experimental colitis [21].
• Developmental platelet endothelial cell adhesion molecule expression suggests multiple roles for a vascular adhesion molecule [22].

Analytical, diagnostic and therapeutic context of Aoc3

• METHODS: We detected VAP-1/SSAO in plasma of diabetic animals, with or without VAP-1 immunoprecipitation, and in culture medium from 3T3-L1 adipocytes and human adipose tissue explants [2].
• Immunohistochemistry demonstrated that the expression of vascular adhesion molecules was significantly increased in cirrhosis [23].
• Moreover, VAP-1 was studied as a potential target to localize inflammation by radioimmunoscintigraphy [24].
• Transgenic expression of human SSAO in tissues with a high content of smooth muscle cells was confirmed by Northern blot analysis [25].
• [14C]MA following intravenous injection would be quickly metabolized by SSAO [26].

References