Aldose reductase in the etiology of diabetic complications: 2. Nephropathy

Stribling, Donald; Armstrong, Frank M.; Harrison, H E

doi:10.1016/0891-6632(89)90015-9

Cited by 14 publications

(10 citation statements)

References 53 publications

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“…Other major mechanisms that have been shown in cell culture models and animal models of diabetes to be of importance include the following: oxidative stress, activation of the serine/threonine kinase-protein kinase C β leads to alterations in cell function and cell survival [19][20][21]; advanced glycation end products, which are produced by a nonenzymatic glycation of susceptible amino acids and alter enzyme structure and function [22,23], and transforming growth factor-β, which causes fibrosis [20,24]; in addition, increased aldose reductase presumably due to increased influx of glucose, which leads to both an increase in sorbitol, which may be pathogenic, and to consumption of NADPH, which leads to oxidative stress (discussed below) [25]. There is also growing evidence for pathologic roles for matrix metalloproteinases [26], Notch signaling [27], WNT/β catenin [28], genetic predisposition [29], and others.…”

Section: Pathophysiologymentioning

confidence: 98%

Oxidative Stress and Diabetic Kidney Disease

Stanton

2011

Curr Diab Rep

104

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The number of people with diabetic kidney disease continues to increase worldwide despite current treatments. Of the pathophysiologic mechanisms that have been identified in the development and progression of diabetic nephropathy, oxidative stress (more accurately described as increased levels of reactive oxygen species; ROS) is of major importance. The increase in ROS is due to both increased production and to decreased and/or inadequate antioxidant function. To date, human clinical trials with antioxidants have not been shown to be effective. This is likely due, at least in part, to the lack of specificity of current agents. Recent research has determined both major sources of high glucose-induced cellular ROS production as well as high glucose-induced changes in antioxidant function. Treatments targeted at one or more of the specific diabetes-induced alterations in the regulation of ROS levels will likely lead to effective treatments that prevent the development and progression of diabetic kidney disease.

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Section: Pathophysiologymentioning

confidence: 98%

Oxidative Stress and Diabetic Kidney Disease

Stanton

2011

Curr Diab Rep

104

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“…Both MI depletion and polyol accumulation have been cited as contributing factors in the devastating complications associated with diabetes (e.g., neuropathy, retinopathy, and nephropathy) 34. For these reasons, MIOX has been touted as a potential target for treatment of diabetic complications 36–41…”

Section: Discovery and Physiology Of Mioxmentioning

confidence: 99%

myo-Inositol oxygenase: a radical new pathway for O₂and C–H activation at a nonheme diiron cluster

et al. 2009

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The enzyme myo-inositol oxygenase (MIOX) catalyzes conversion of myo-inositol (cyclohexan-1,2,3,5/4,6-hexa-ol or MI) to D-glucuronate (DG), initiating the only known pathway in humans for catabolism of the carbon skeleton of cell-signaling inositol (poly)phosphates and phosphoinositides. Recent kinetic, spectroscopic, and crystallographic studies have shown that the enzyme activates its substrates, MI and O 2 , at a carboxylate-bridged nonheme diiron(II/III) cluster, making it the first of many known nonheme diiron oxygenases to employ the mixed-valent form of its cofactor. Evidence suggests that (1) the Fe(III) site coordinates MI via its C1 and C6 hydroxyl groups, (2) the Fe(II) site reversibly coordinates O 2 to produce a superoxo-diiron(III/III) intermediate, and (3) the pendant oxygen atom of the superoxide ligand abstracts hydrogen from C1 to initiate the unique C-C-bond-cleaving, four-electron oxidation reaction. This review recounts the studies leading to the recognition of the novel cofactor requirement and catalytic mechanism of MIOX and forecasts how remaining gaps in our understanding might be filled by additional experiments.Bacterial multi-component monooxygenases [BMMs; e.g., soluble methane monooxygenase (sMMO), toluene/o-xylene monooxygenase (ToMO), and phenol hydroxylase], plant fatty acyl desaturases (e.g., stearoyl acyl carrier protein Δ 9 -desaturase) and the R2 subunits of conventional class I ribonucleotide reductases (RNR-R2s) all use carboxylate-bridged dinuclear iron clusters to activate O 2 for cleavage of strong C-H or O-H bonds. 1-5 Each of these reaction begins with the reduction of O 2 to the peroxide oxidation state by the diiron(II/ II) form of the cofactor. In several cases, peroxide-bridged diiron(III/III) intermediates have been directly characterized. 6-11 Several of the peroxide complexes are known or believed to undergo O-O-bond cleavage to generate high-valent iron complexes that cleave the target C/ O-H bonds. 1-5 For example, the diiron(III/IV) complex, X, in the RNR-R2 reaction oxidizes a tyrosine residue by one electron, cleaving the phenolic O-H bond and activating the protein for participation in nucleotide reduction with its partner subunit, RNR-R1. [12][13][14][15][16][17][18][19][20][21] Similarly, the diiron(IV/IV) complex, Q, in the sMMO reaction cleaves a C-H bond of methane to initiate its hydroxylation. 1,3,7,[22][23][24] In each of these reactions, a diiron(III/III) form of the cluster is generated at the end of the oxidation sequence. For the reactions that are catalytic, a complete "turnover" therefore requires reduction of the cluster back to the O 2 -reactive diiron(II/II) state by additional proteins, with electrons provided ultimately by NAD(P)H. 1,3,4 Although this Please send correspondence to: J.

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“…In addition, focal and segmental GS has been described in association with experimental diabetes (2,3,5). The pathogenesis of diabetic glomerulopathy may be directly related to the attending metabolic disturbance via such phenomena as nonenzymatic glycosylation (13) and sorbitol accumulation (14). However, glomerular hemodynamic factors may also play a pivotal role in this process as recently suggested by several experimental studies (2,3,5).…”

mentioning

confidence: 91%

Glomerular Abnormalities in Long-Term Experimental Diabetes: Role of Hemodynamic and Nonhemodynamic Factors and Effects of Antihypertensive Therapy

1992

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To evaluate the role of glomerular hypertension, glomerular hypertrophy, glomerular lipid deposition, and plasma cholesterol levels in diabetic glomerulopathy, Munich-Wistar rats received streptozocin and daily insulin injections and were assigned to one of three groups: untreated diabetic (DMC), hydralazine-treated diabetic (DMH), and enalapril-treated diabetic (DME). Age-matched control rats were also studied. At 6-10 wk of diabetes, DMC rats showed marked elevations of glomerular pressure and glomerular filtration rate as well as slight glomerular enlargement and cholesterol elevation. DMH and DME rats exhibited arterial hypotension but no change in cholesterol or glomerular volume. Glomerular pressure was normalized by enalapril but not by hydralazine treatment. Additional rats were followed up to 12 mo of diabetes. Slight hypertension was seen in DMC rats, whereas sustained hypotension occurred in DMH and DME rats. Progressive albuminuria occurred in DMC and DMH but not in DME rats. At 12 mo, glomerular hypertension persisted in DMC and DMH rats but was still absent in DME rats. Cholesterol was elevated in DMC and slightly lower in DMH and DME rats. Glomeruli were equally enlarged in the diabetic groups. Glomerular sclerotic lesions and lipid deposits appeared in DMC and DMH but not in DME rats. These findings are consistent with the notion that glomerular hypertension may promote glomerular injury in experimental diabetes. Glomerular lipid deposition may also participate in this process, although a causal relationship was not demonstrated. Glomerular hypertrophy and cholesterol were unrelated to glomerular injury, although they may have exacerbated hemodynamically mediated damage.

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Aldose reductase in the etiology of diabetic complications: 2. Nephropathy

Cited by 14 publications

References 53 publications

Oxidative Stress and Diabetic Kidney Disease

Oxidative Stress and Diabetic Kidney Disease

myo-Inositol oxygenase: a radical new pathway for O₂and C–H activation at a nonheme diiron cluster

Glomerular Abnormalities in Long-Term Experimental Diabetes: Role of Hemodynamic and Nonhemodynamic Factors and Effects of Antihypertensive Therapy

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Aldose reductase in the etiology of diabetic complications: 2. Nephropathy

Cited by 14 publications

References 53 publications

Oxidative Stress and Diabetic Kidney Disease

Oxidative Stress and Diabetic Kidney Disease

myo-Inositol oxygenase: a radical new pathway for O2and C–H activation at a nonheme diiron cluster

Glomerular Abnormalities in Long-Term Experimental Diabetes: Role of Hemodynamic and Nonhemodynamic Factors and Effects of Antihypertensive Therapy

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myo-Inositol oxygenase: a radical new pathway for O₂and C–H activation at a nonheme diiron cluster