title: Semicarbazide-sensitive amine oxidase (SSAO) gene expression in alloxan-induced diabetes in mice.
abstract: BACKGROUND
  Plasma activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be significantly higher in diabetic patients compared to healthy controls. Due to the production of highly angiotoxic substances in SSAO-catalyzed reactions, it has been speculated that this could be a cause for the vascular complications frequently associated with diabetes. Little is known about how the enzyme activity is regulated, and why it is high in these patients. 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.
  
  
  METHODS
  Diabetes was induced in NMRI mice by a single intravenous injection of alloxan. The enzyme activity was analyzed by a radiometric assay using (14) C-benzylamine as a substrate, and the mRNA-levels were analyzed by real-time PCR.
  
  
  RESULTS
  We found that the enzyme activity was increased in lung and adipose tissue 1 day after induction, as the glucose levels start to rise. Seven days after the injection of alloxan, the activity in serum was increased, and this activity was positively correlated with blood glucose levels in the alloxan-treated animals. Although the enzyme activity was increased in adipose tissue as a result of the treatment, SSAO-mRNA levels in this tissue were decreased, possibly suggesting a negative feedback on the gene expression.
  
  
  CONCLUSIONS
  The main conclusion from this study is that the increased enzyme activity observed in diabetes is not a result of increased SSAO gene transcription. We speculate that the enzyme activity is controlled by posttranslational modifications of the protein, and that the catalytic activity controls the gene expression.
authors.affiliation: Department of Neuroscience, Unit of Pharmacology, Uppsala University, Uppsala, Sweden. Jenny.Norsquist@neuro.uu.se
authors.forename: Jenny E L
authors.initials: JE
authors.lastname: Nordquist
authors.forename: Camilla
authors.initials: C
authors.lastname: Göktürk
authors.forename: Lars
authors.initials: L
authors.lastname: Oreland
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000496:Alloxan; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002230:Carbidopa / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D006830:Hydralazine / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D012333:RNA, Messenger; D006830:Hydralazine; D000496:Alloxan; D006631:Amine Oxidase (Copper-Containing); D002230:Carbidopa