Tissue distribution of mammalian aldose reductase and related enzymes

Markus, H.; Raducha, Michael; Harris, Harry

doi:10.1016/0006-2944(83)90051-0

Cited by 44 publications

(15 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…One such possibility is that AR is expressed at very low levels in mice compared with humans (46,47). AR catalyzes the reaction of glucose to sorbitol and produces reactive oxygen species in cultured cells (7).…”

Section: Discussionmentioning

confidence: 99%

Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis

Vikramadithyan

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

The factors underlying cardiovascular risk in patients with diabetes have not been clearly elucidated. Efforts to study this in mice have been hindered because the usual atherogenic diets that contain fat and cholesterol also lead to obesity and insulin resistance. We compared plasma glucose, insulin, and atherosclerotic lesion formation in LDL receptor knockout (Ldlr 2/2 ) mice fed diets with varying fat and cholesterol content that induced similar lipoprotein profiles. Ldlr 2/2 mice fed a high-fat diet developed obesity, mild hyperglycemia, hyperinsulinemia, and hypertriglyceridemia. Quantitative and qualitative assessments of atherosclerosis were unchanged in diabetic Ldlr 2/2 mice fed a high-fat diet compared with lean nondiabetic control mice after 20 weeks of diet. Although one group of mice fed diets for 40 weeks had larger lesions at the aortic root, this was associated with a more atherogenic lipoprotein profile. The presence of a human aldose reductase transgene had no effect on atherosclerosis in fat-fed Ldlr 2/2 mice with mild diabetes. Our data suggest that when lipoprotein profiles are similar, addition of fat to a cholesterol-rich diet does not increase atherosclerotic lesion formation in Ldlr 2/2

show abstract

Section: Discussionmentioning

confidence: 99%

Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis

Vikramadithyan

et al. 2006

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…3 AR expression and activity have been described in various tissues including the lens of the eye, kidney, and nerve in several animal models including rat, rabbit, and pig. 28 A causal relation between metabolization of glucose by AR and diabetic complications was shown in several animal models of cataract 29 and renal dysfunction 30 or neuropathy. 31 Similarly, AR activity has been associated with cataract, 10 nephropathy, 11 and polyneuropathy 12 in diabetic patients.…”

Section: Gleissner Et Al Aldose Reductase In Foam Cells 1141mentioning

confidence: 98%

Upregulation of Aldose Reductase During Foam Cell Formation as Possible Link Among Diabetes, Hyperlipidemia, and Atherosclerosis

Gleissner

Sanders

Nadler

et al. 2008

ATVB

View full text Add to dashboard Cite

Objective-Aldose reductase (AR) is the rate-limiting enzyme of the polyol pathway. In diabetes, it is related to microvascular complications. We discovered AR expression in foam cells by gene chip screening and hypothesized that it may be relevant in atherosclerosis. Methods and Results-AR gene expression and activity were found to be increased in human blood monocyte-derived macrophages during foam cell formation induced by oxidized LDL (oxLDL, 100 g/mL). AR activity as photometrically determined by NADPH consumption was effectively inhibited by the AR inhibitor epalrestat. oxLDL-dependent AR upregulation was further increased under hyperglycemic conditions (30 mmol/L D-glucose) as compared to osmotic control, suggesting a synergistic effect of hyperlipidemia and hyperglycemia. AR was also upregulated by 4-hydroxynonenal, a constituent of oxLDL. Upregulation was blocked by an antibody to CD36. AR inhibition resulted in reduction of oxLDL-induced intracellular oxidative stress as determined by 2Ј7Ј-dichlorofluoresceine diacetate (H 2 DCFDA) fluorescence, indicating that proinflammatory effects of oxLDL are partly mediated by AR.

show abstract

“…Wilson et al (1992) predict the substrate-binding site may exist in a region with fewer conserved residues compared to the residues forming the cofactor-binding site. In general, aldehyde reductase prefers aromatic aldehydes as substrates (Markus, Raducha & Harris, 1983). It is possible that the differences in the residues forming the substrate-binding pocket for aldose and aldehyde reductase may be responsible for differences in substrate specificities.…”

Section: Residue Numbermentioning

confidence: 99%

Structures of human and porcine aldehyde reductase: an enzyme implicated in diabetic complications

El‐Kabbani

Green²,

Lin³

et al. 1994

Acta Cryst D

View full text Add to dashboard Cite

The crystal structures of porcine and human aldehyde reductase, an enzyme implicated in complications of diabetes, have been determined by X-ray diffraction methods. The crystallographic R factor for the refined porcine aldehyde reductase model is 0.19 at 2.8 A resolution. There are two molecules in the asymmetric unit related by a local non-crystallographic twofold axis. The human aldehyde reductase model has been refined to an R factor of 0.21 at 2.48 A resolution. The amino-acid sequence of porcine aldehyde reductase revealed a remarkable homology with human aldehyde reductase. The coenzyme-binding site residues are conserved and adopt similar conformations in human and porcine aldehyde reductase apo-enzymes. The tertiary structures of aldhyde reductase and aldose reductase are similar and consist of a fl/a-barrel, with the coenzyme-binding site located at the carboxyterminus end of the strands of the barrel. The crystal structure of porcine and human aldehyde reductase should allow in vitro mutagenesis to elucidate the mechanism of action for this enzyme and facilitate the effective design of specific inhibitors.

show abstract

Tissue distribution of mammalian aldose reductase and related enzymes

Cited by 44 publications

References 29 publications

Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis

Addition of dietary fat to cholesterol in the diets of LDL receptor knockout mice: effects on plasma insulin, lipoproteins, and atherosclerosis

Upregulation of Aldose Reductase During Foam Cell Formation as Possible Link Among Diabetes, Hyperlipidemia, and Atherosclerosis

Structures of human and porcine aldehyde reductase: an enzyme implicated in diabetic complications

Contact Info

Product

Resources

About