Autoradiographic imaging of formaldehyde adducts in mice: possible relevance for vascular damage in diabetes.
The activity of semicarbazide-sensitive amine oxidase (SSAO) has been reported to be elevated in blood from diabetic patients. It has been suggested that the enzyme is involved in the development of complications such as retinopathies, nephropathies and neuropathies, which are associated with advanced diabetes, possibly by the formation of toxic metabolites. Under the influence of SSAO, methylamine is deaminated to formaldehyde which is known to react with various macromolecules. It has therefore been proposed that specific inhibition of SSAO could be of therapeutic value for treatment of diabetic patients. The present results provide evidence that treatment with an SSAO inhibitor potently reduces the levels of irreversible adducts. In this study, 14C-methylamine was given intraperitoneally to NMRI mice, and the tissue distribution of irreversibly bound methylamine metabolites was estimated by an autoradiographic method. Such radioactive residues occurred in high concentrations in the intestinal wall, brown adipose tissue, spleen and bone marrow. By inhibiting SSAO irreversibly with hydralazine before giving 14C-methylamine to the mice, it was possible to determine the resynthesis rate of SSAO in different tissues. A complete recovery of SSAO activity was seen in the intestinal wall after 6 days, whereas only about 60% was recovered in adipose tissue after 14 days. This suggests that factors controlling the synthesis of SSAO differ in these tissues, or that these tissues express different forms of enzymes.
Grönvall
J L
JL
Department of Neuroscience (Pharmacology), Uppsala University, Biomedical Center, Sweden.
Garpenstrand
H
H
Oreland
L
L
Ekblom
J
J
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D003641:Deamination; D003920:Diabetes Mellitus / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005557:Formaldehyde / Q000378:metabolism*; D006830:Hydralazine / Q000494:pharmacology; D008297:Male; D008744:Methylamines / Q000378:metabolism*; D051379:Mice; D010084:Oxidation-Reduction; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D014018:Tissue Distribution
D004791:Enzyme Inhibitors; D008744:Methylamines; D005557:Formaldehyde; D006830:Hydralazine; C027451:methylamine; D006631:Amine Oxidase (Copper-Containing); D000587:Oxidoreductases Acting on CH-NH Group Donors