title: Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome.
abstract: OBJECTIVE
  Methylglyoxal (MG) overproduction has been reported in metabolic syndrome with hyperglycaemia (diabetes) or without hyperglycaemia (hypertension), and the underlying mechanism was investigated.
  
  
  RESULTS
  Contributions of different pathways or enzymes to MG formation were evaluated in aorta or cultured vascular smooth muscle cells (VSMCs). In all four animal models of metabolic syndrome, i.e. chronically fructose-fed hypertensive Sprague-Dawley rats, spontaneously hypertensive rats, obese non-diabetic Zucker rats, and diabetic Zucker rats, serum and aortic MG and fructose levels were increased, and the expression of GLUT5 (transporting fructose) and aldolase B (converting fructose to MG) in aorta were up-regulated. Aortic expressions of aldolase A, semicarbazide-sensitive amine oxidase (SSAO), and cytochrome P450 2E1 (CYP 2E1), accounting for MG formation during glycolysis, protein, and lipid metabolism, respectively, was unchanged/reduced. Fructose (25 mM) treatment of VSMCs up-regulated the expression of GLUT5 and aldolase B and accelerated MG formation. Insulin (100 nM) increased GLUT5 expression and augmented fructose-increased cellular fructose accumulation and MG formation. Glucose (25 mM) treatment activated the polyol pathway and enhanced fructose formation, leading to aldolase B upregulation and MG overproduction. Inhibition of the polyol pathway reduced the glucose-increased aldolase B expression and MG generation. The excess formation of MG in under these conditions was eliminated by knock-down of aldolase B, but not by knock-down of aldolase A or inhibition of SSAO or CYP 2E1.
  
  
  CONCLUSIONS
  Upregulation of aldolase B by accumulated fructose is a common mechanism for MG overproduction in VSMCs and aorta in different models of metabolic syndrome.
authors: Department of Pharmacology,  College of Medicine, University of Saskatchewan, A120 Health Sciences Building, 107 Wiggins Road, Saskatoon, SK,  Canada S7N 5E5.
authors: Jianghai
authors: J
authors: Liu
authors: Rui
authors: R
authors: Wang
authors: Kaushik
authors: K
authors: Desai
authors: Lingyun
authors: L
authors: Wu
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000201:enzymology; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000378:metabolism; D065691:Cytochrome P-450 CYP2E1 Inhibitors; D003920:Diabetes Mellitus / Q000378:metabolism; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism; D005634:Fructose-Bisphosphate Aldolase / Q000235:genetics / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D051296:Glucose Transporter Type 5 / Q000378:metabolism; D006973:Hypertension / Q000201:enzymology; D007064:L-Iditol 2-Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000201:enzymology* / Q000235:genetics; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D032389:Myocytes, Smooth Muscle / Q000201:enzymology*; D009765:Obesity / Q000201:enzymology; D011765:Pyruvaldehyde / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation
chemical_list: D065691:Cytochrome P-450 CYP2E1 Inhibitors; D004791:Enzyme Inhibitors; D051296:Glucose Transporter Type 5; D012333:RNA, Messenger; C495727:Slc2a5 protein, rat; D005632:Fructose; D011765:Pyruvaldehyde; D007064:L-Iditol 2-Dehydrogenase; D000449:Aldehyde Reductase; D019392:Cytochrome P-450 CYP2E1; D006631:Amine Oxidase (Copper-Containing); D005634:Fructose-Bisphosphate Aldolase; D005947:Glucose