RGD Reference Report - Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome. - Rat Genome Database

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Upregulation of aldolase B and overproduction of methylglyoxal in vascular tissues from rats with metabolic syndrome.

Authors: Liu, Jianghai  Wang, Rui  Desai, Kaushik  Wu, Lingyun 
Citation: Liu J, etal., Cardiovasc Res. 2011 Dec 1;92(3):494-503. doi: 10.1093/cvr/cvr239. Epub 2011 Sep 2.
RGD ID: 13673877
Pubmed: (View Article at PubMed) PMID:21890532
DOI: Full-text: DOI:10.1093/cvr/cvr239

AIMS: Methylglyoxal (MG) overproduction has been reported in metabolic syndrome with hyperglycaemia (diabetes) or without hyperglycaemia (hypertension), and the underlying mechanism was investigated.
METHODS AND 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.
CONCLUSION: Upregulation of aldolase B by accumulated fructose is a common mechanism for MG overproduction in VSMCs and aorta in different models of metabolic syndrome.

Disease Annotations    
Metabolic Syndrome  (IEP,ISO)

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Aldoa  (aldolase, fructose-bisphosphate A)

Genes (Mus musculus)
Aldoa  (aldolase A, fructose-bisphosphate)

Genes (Homo sapiens)
ALDOA  (aldolase, fructose-bisphosphate A)

Additional Information