Disease relevance of Aoc3

• Rat cytomegalovirus infection in kidney allograft recipients is associated with increased expression of intracellular adhesion molecule-1 vascular adhesion molecule-1, and their ligands leukocyte function antigen-1 and very late antigen-4 in the graft [1].
• Semicarbazide-sensitive amine oxidase substrates potentiate hydralazine hypotension: possible role of hydrogen peroxide [2].
• This study demonstrates that developmental toxicity, characterized by striking vascular lesions and dilated thoracic aortas, can result from specific in vivo SSAO inhibition, suggesting a role for SSAO in connective tissue matrix development and maintenance, and specifically in the development of normal elastin [3].
• RESULTS: Relative expression of intercellular adhesion molecule-1, vascular adhesion molecule-1, interleukin-1beta, and interleukin-6 mRNAs differed significantly (2.4 -4.6 times higher) between brain-dead and control hearts (p < 0.05; group t-test) [4].
• These results suggest the possibility that elevated methylamine found in several pathologic states (such as uremia and diabetes mellitus), or generated from exogenous sources, could result in overproduction of formaldehyde in tissues with high SSAO activity, especially blood vessels [5].

High impact information on Aoc3

• Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage [6].
• Vascular adhesion molecule-1 and intercellular adhesion molecule-1 expression on rat liver cells after lipopolysaccharide administration in vivo [7].
• Blockade of vascular adhesion protein-1 inhibits lymphocyte infiltration in rat liver allograft rejection [8].
• In addition to caveolins, the structural components of caveolae, their major protein constituents, are the semicarbazide-sensitive amine oxidase and the scavenger lipoprotein receptor CD36 [9].
• The improvement caused by benzylamine plus vanadate was abolished when rats were pretreated with the SSAO-inhibitor semicarbazide [10].

Chemical compound and disease context of Aoc3

• We hypothesized that inhibitors of SSAO might reduce the acute cardiovascular toxicity of allylamine [11].
• 2-bromoethylamine, a suicide inhibitor of semicarbazide-sensitive amine oxidase, increases hydralazine hypotension in rats [12].
• The role of plasma semicarbazide-sensitive amine oxidase in allylamine and beta-aminopropionitrile cardiovascular toxicity: mechanisms of myocardial protection and aortic medial injury in rats [13].
• BACKGROUND: A chemical-induced, nonlethal, dissecting aortic aneurysm (DAA) is described following in utero exposure to semicarbazide, an inhibitor of the vascular enzyme semicarbazide sensitive amine oxidase (SSAO) [14].
• The deamination of methylamine and aminoacetone by semicarbazide-sensitive amine oxidase (SSAO) produces formaldehyde and methylglyoxal, respectively, which have been presumed to be involved in diabetic complications [15].

Biological context of Aoc3

• Semicarbazide-sensitive amine oxidase (SSAO) (EC 1.4.3.6) is widely distributed in nature and catalyzes the oxidative deamination of primary amines [16].
• The deduced amino acid sequence showed 91% and 80% identity with mouse and human SSAO, respectively [16].
• In this study we isolated full-length SSAO cDNA from rat aorta and examined its mRNA expression in various rat tissues by real-time PCR, as well as the subcellular and tissue distributions of SSAO activity [16].
• Poly IC induced islet cell Class I hyperexpression, up regulation of pancreatic endothelial intercellular adhesion molecule-1 and vascular adhesion molecule-1 and a T-cell and macrophage infiltration of the pancreatic interstitium in all rat strains studied, including diabetes-resistant strains [17].
• Exogenously added H(2)O(2) was initially found to inhibit the synthesis of NOS2, which prompted us to assess the effect of the activity of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) as H(2)O(2)-forming enzymes on NOS2 gene expression [18].

Anatomical context of Aoc3

• Thus, a high level of SSAO was shown in adipocytes by both mRNA expression and enzyme activity measurement [16].
• SSAO activity and immunoreactive SSAO protein were maximal in plasma membranes, and they were also detectable in intracellular membranes [19].
• Adipocyte membranes had substantial levels of semicarbazide-sensitive amine oxidase (SSAO) [19].
• SSAO activity was also found in GLUT4 vesicles from 3T3-L1 adipocytes and rat skeletal muscle [19].
• We also measured the effect of high glucose on the expression of intercellular adhesion molecule-1 and vascular adhesion molecule-1 by flow cytometry and semiquantitative RT-PCR in mesangial cells and the adhesion of leukocytes to mesangial cells [20].

Associations of Aoc3 with chemical compounds

• Role of semicarbazide-sensitive amine oxidase on glucose transport and GLUT4 recruitment to the cell surface in adipose cells [19].
• This synergistic effect of benzylamine and vanadate on glucose transport was totally abolished in the presence of semicarbazide, a specific inhibitor of SSAO [19].
• Neither vascular adhesion molecule-1 protein nor mRNA expression was, however, affected by high glucose and high mannitol [20].
• Pargyline and semicarbazide, specific inhibitors of MAO and SSAO, respectively, canceled this negative effect of MAO substrates on NOS2 expression [18].
• The kinetic pattern of inactivation of SSAO by hydralazine is consistent with an active-site-directed site-saturable binding followed by the development of an irreversible enzyme-inhibitor complex [21].

Regulatory relationships of Aoc3

• Interleukin-1-beta (IL-1beta) can promote inflammation by up-regulating vascular adhesion molecules and inhibit inflammation by activating the hypothalamic-pituitary-adrenal (HPA) axis to produce anti-inflammatory glucocorticoids [22].

Other interactions of Aoc3

• Studies of monoamine oxidase and semicarbazide-sensitive amine oxidase. I. Inhibition by a selective monoamine oxidase-B inhibitor, MD 780236 [23].
• This was associated with a decreased influx of leukocytes into the cerebrospinal fluid, which occurred despite an elevated production of relevant chemokines (e.g., macrophage-inflammatory protein-2) and a higher expression of vascular adhesion molecules (e.g., VCAM-1) [24].
• A continuous, peroxidase-linked spectrophotometric assay is described which is suitable for measuring monoamine and diamine oxidase and semicarbazide-sensitive amine oxidase activities in tissue homogenates [25].
• Inhibition of monoamine oxidase A-form and semicarbazide-sensitive amine oxidase by selective and reversible monoamine oxidase-A inhibitors, amiflamine and FLA 788(+) [26].
• Semicarbazide-sensitive amine oxidase and extracellular matrix deposition by smooth-muscle cells [27].

Analytical, diagnostic and therapeutic context of Aoc3

• Molecular cloning and characterization of rat semicarbazide-sensitive amine oxidase [16].
• 3H-labelled material solubilized from [3H]hydralazine-treated membrane pellets by Triton X-100 at that detergent/protein ratio which releases SSAO from membranes shows the same gel-filtration characteristics as SSAO and appears by lentil lectin-agarose affinity chromatography to contain similar carbohydrate moieties [21].
• The glycoprotein nature of SSAO was established from affinity chromatography with either immobilized concanavalin A or Lens culinaris lectin [28].
• In the presence of their substrates, tyramine for MAO and benzylamine for SSAO, intracellular synthesis of H(2)O(2) took place with concomitant inhibition of LPS/IFN-gamma-induced NOS2 protein synthesis, as detected by Western blotting, flow cytometry, and immunofluorescence microscopy analyses [18].
• 2. Inhibition of SSAO by treating rats with 1 mg kg-1 (E)-2-(3',4'-dimethoxyphenyl)-3-fluoroally lamine (MDL 72145) 1 h before dissection, had no significant effect on the maximum pressure attained or the area under the curve (AUC) of the response to both low and high doses of Tyr [29].

References