<i>Suppression of Renal α‐Dicarbonyl Compounds Generated following Ureteral Obstruction by Kidney‐Specific α‐Dicarbonyl/<scp>l</scp>‐Xylulose Reductase</i>

Odani, Hiroko; Asami, Jun; Ishii, Aiko; Oide, Kayoko; Sudo, Takako; Nakamura, Atsushi; Miyata, Noriyuki; Otsuka, Noboru; Maeda, Kenji; Nakagawa, Junichi

doi:10.1196/annals.1433.003

Cited by 14 publications

(11 citation statements)

References 6 publications

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“…It is hypothesized that reduction of dicarbonyl compounds by DCXR could provide a detoxification function and result in reduced advanced glycation end-product accumulation (13). Consistent with this hypothesis, it was found that renal α-dicarbonyl compounds were decreased in DCXR-transgenic mice after renal unilateral ureteral obstruction (35), and that diabetic symptoms were reduced when DCXR-transgenic mice were crossed to the KK-A y diabetic model (36). These results suggest that the level of xylulose reductase activity may be important under some disease conditions.…”

Section: Discussionmentioning

confidence: 69%

Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria

Pierce

Spurrell

Mandell³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Pentosuria is one of four conditions hypothesized by Archibald Garrod in 1908 to be inborn errors of metabolism. Mutations responsible for the other three conditions (albinism, alkaptonuria, and cystinuria) have been identified, but the mutations responsible for pentosuria remained unknown. Pentosuria, which affects almost exclusively individuals of Ashkenazi Jewish ancestry, is characterized by high levels of the pentose sugar l -xylulose in blood and urine and deficiency of the enzyme l -xylulose reductase. The condition is autosomal-recessive and completely clinically benign, but in the early and mid-20th century attracted attention because it was often confused with diabetes mellitus and inappropriately treated with insulin. Persons with pentosuria were identified from records of Margaret Lasker, who studied the condition in the 1930s to 1960s. In the DCXR gene encoding l -xylulose reductase, we identified two mutations, DCXR c.583ΔC and DCXR c.52(+1)G > A , each predicted to lead to loss of enzyme activity. Of nine unrelated living pentosuric subjects, six were homozygous for DCXR c.583ΔC , one was homozygous for DCXR c.52(+1)G > A , and two were compound heterozygous for the two mutant alleles. l -Xylulose reductase was not detectable in protein lysates from subjects’ cells and high levels of xylulose were detected in their sera, confirming the relationship between the DCXR genotypes and the pentosuric phenotype. The combined frequency of the two mutant DCXR alleles in 1,067 Ashkenazi Jewish controls was 0.0173, suggesting a pentosuria frequency of approximately one in 3,300 in this population. Haplotype analysis indicated that the DCXR c.52(+1)G > A mutation arose more recently than the DCXR c.583ΔC mutation.

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Section: Discussionmentioning

confidence: 69%

Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria

Pierce

Spurrell

Mandell³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…To the contrary, it was reported that in patients with diabetes, the accumulation of AGEs significantly inhibited collagen I biosynthesis on human skin fibroblasts 25,43 . Recently, it was demonstrated that AGEs downregulated the expression of protein and message of type III collagen in rat cardiac fibroblasts and mice kidney cells through multiple signaling pathways, such as MAPK and RAGE 41,44 . These results indicated that the influence of AGEs on collagen synthesis varied with cell type, and the related regulation mechanism remained to be elucidated.…”

Section: Discussionmentioning

confidence: 98%

Advanced Glycation End Products Inhibit the Expression of Collagens Type I and III by Human Gingival Fibroblasts

Ren¹,

Fu²,

Deng³

et al. 2009

Journal of Periodontology

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“…In a search for carbonyl‐metabolizing enzymes that might contribute to the reduction of renal carbonyl stress, the role of Dcxr was investigated using rodent models including mice and rats (Sudo et al , ; Asami et al , ; Odani et al , ). High expression of mouse Dcxr in the brush border epithelium of renal tubules was described previously (Nakagawa et al , ) and implied a potential role in the detoxification of AGE‐precursors in the kidney.…”

Section: Catalytic Activity Of Human Dcxrmentioning

confidence: 99%

Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

Ebert¹,

Kisiela²,

Maser³

2014

Biological Reviews

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Dicarbonyl/L-xylulose reductase (DCXR; SDR20C1), a member of the short-chain dehydrogenase/reductase (SDR) superfamily catalyzes the reduction of α-dicarbonyl compounds and monosaccharides. Its role in the metabolism of L-xylulose has been known since 1970, when essential pentosuria was found to be associated with DCXR deficiency. Despite its early discovery, our knowledge about the role of human DCXR in normal physiology and pathophysiology is still incomplete. Sporadic studies have demonstrated aberrant expression in several cancers, but their physiological significance is unknown. In reproductive medicine, where DCXR is commonly referred to as 'sperm surface protein P34H', it serves as marker for epididymal sperm maturation and is essential for gamete interaction and successful fertilization. DCXR exhibits a multifunctional nature, both acting as a carbonyl reductase and also performing non-catalytic functions, possibly resulting from interactions with other proteins. Recent observations associate DCXR with a role in cell adhesion, pointing to a novel function involving tumour progression and possibly metastasis. This review summarizes the current knowledge about human DCXR and its orthologs from mouse and Caenorhabditis elegans (DHS-21) with an emphasis on its multifunctional characteristics. Due to its close structural relationship with DCXR, carbonyl reductase 2 (Cbr2), a tetrameric enzyme found in several non-primate species is also discussed. Similar to human DCXR, Cbr2 from golden hamster (P26h) and cow (P25b) is essential for sperm-zona pellucida interaction and fertilization. Because of the apparent similarity of these two proteins and the inconsistent use of alternative names previously, we provide an overview of the systematic classification of DCXR and Cbr2 and a phylogenetic analysis to illustrate their ancestry.

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Suppression of Renal α‐Dicarbonyl Compounds Generated following Ureteral Obstruction by Kidney‐Specific α‐Dicarbonyl/l‐Xylulose Reductase

Cited by 14 publications

References 6 publications

Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria

Garrod's fourth inborn error of metabolism solved by the identification of mutations causing pentosuria

Advanced Glycation End Products Inhibit the Expression of Collagens Type I and III by Human Gingival Fibroblasts

Human DCXR – another ‘moonlighting protein’ involved in sugar metabolism, carbonyl detoxification, cell adhesion and male fertility?

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