Kinetic studies of AKR1B10, human aldose reductase-like protein: Endogenous substrates and inhibition by steroids

Endo, Shunsuke; Matsunaga, Toshiyuki; Mamiya, Hiroaki; Ohta, Chisato; Soda, Midori; Kitade, Yukio; Tajima, Kazuo; Zhao, Hai-Tao; El‐Kabbani, Ossama; Hara, Akira

doi:10.1016/j.abb.2009.05.009

Cited by 94 publications

(148 citation statements)

References 54 publications

Supporting

Mentioning

145

Contrasting

Order By: Relevance

“…Compared to the broad substrate specificity of AR and other ARLPs (AKR1B10, AKR1B8 and AKR1B13), 2,13,32) AKR1B7 has been studied with limited substrates, which are some aliphatic aldehydes (HNE and isocaproaldehyde), a-di- carbonyl compounds (methylglyoxal and diacetyl) and aldoses (glucose and xylose), 10,12) in addition to 4-nitrobenzaldehyde and PGH 2 .…”

mentioning

confidence: 99%

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Endo

Matsunaga

Fujita

et al. 2010

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

The aldo-keto reductase (AKR) superfamily is a rapidly growing group of pyridine nucleotide-dependent oxidoreductases that metabolize carbohydrates, steroids, prostaglandins, and other endogenous aldehydes and ketones, as well as xenobiotic compounds.1,2) Aldose reductase (AR), which belongs to the AKR1B subfamily, is a nicotinamide adenine dinucleotide phosphate reduced form (NADPH)-dependent enzyme that catalyses the first step in the polyol pathway and has been implicated in the onset of secondary complications of diabetes in humans.3,4) AR shows broad substrate specificity for various aldehydes and aldoses, and is involved in various physiological roles, including the metabolism of retinoids, steroids and xenobiotics, and defensive mechanisms for oxidative stress. [5][6][7][8] Beside AR, multiple AR-like proteins (ARLPs) that show high sequence similarity (67-71%) to ARs have been identified in human and rodent tissues. While one ARLP (AKR1B10) is ubiquitously expressed in human tissues, 8,9) two ARLPs, androgen-dependent vas deferens protein (AKR1B7) 10) and fibroblast growth factor-inducible protein (AKR1B8), 11) are distributed tissue-specifically in mice. The two mouse ARLPs reduce aldehydes, but are clearly distinct from mouse AR in their poor efficiency in reducing glucose.12,13) AKR1B7 and AKR1B8 differ in their substrate specificity and inhibitor sensitivity. Compared to AKR1B7, 10,12) AKR1B8 exhibits high catalytic efficiency for cytotoxic 4-hydroxynonenal (HNE) derived from lipid peroxidation, 13) but has poor reactivity towards isocaproaldehyde resulting from the side chain cleavage of cholesterol during steroidogenesis.10) AKR1B7 is insensitive to AR inhibitors (ARIs) 10) and exhibits prostaglandin (PG) F 2a synthase activity, which is not detected in the ARI-sensitive AKR1B8. 14)In rats, two ARLPs, AKR1B13 and AKR1B14, have been identified, 15,16) and are thought to be orthologs of mouse AKR1B8 and AKR1B7, respectively, based on high sequence identity of 95% (AKR1B13 versus AKR1B8) and 87% (AKR1B14 versus AKR1B7). AKR1B13 is distributed in almost all rat tissues, and exhibits similar substrate specificity and inhibitor sensitivity to AKR1B8. 17) AKR1B14 and AKR1B7 are similar in their high expression in the adrenal glands and induction by adrenocorticotropic hormone, 10,16,18) but differ in their distribution and gene regulation in other tissues. AKR1B7 is also expressed in mouse vas deferens, intestine and liver, and is up-regulated by androgen, pituitary tropic hormones and agonists of nuclear receptors (liver X receptor-a, pregnane X receptor and constitutive androstane receptor). 10,19,20) In contrast, AKR1B14 is highly expressed in female rat liver through female-specific secretion pattern of growth hormone, 21) and its expression in male rat liver is up-regulated by oxidative stress. 22) Thus, these differences have suggested that AKR1B14 plays a physiological role distinct from its mouse ortholog, AKR1B7. However, there is no report on the detailed properties of AKR1B14, except for its ro...

show abstract

mentioning

confidence: 99%

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Endo

Matsunaga

Fujita

et al. 2010

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

show abstract

“…AKR1B10 is a NADPH-dependent oxidoreductase and reduces various aldehydes and ketones, including endogenous substrates such as retinals, farnesal and geranylgeranial (2,3). AKR1B10 is, however, highly expressed in several types of cancers, including hepatocellular carcinoma (4), lung squamous cell carcinoma, lung adnocarcinoma in smokers (5) and cervical cancer (6).…”

Section: Introductionmentioning

confidence: 99%

Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10

Song¹,

Lee²,

Lee³

et al. 2010

BMB Reports

View full text Add to dashboard Cite

Aldo-keto reductase family 1 B10 (AKR1B10) is a member of the NADPH-dependent aldo-keto reductase (AKR) superfamily, and has been considered to be a potential cancer therapeutic target. Total extract from the bark of Rhus verniciflua (Toxicodendron vernicifluum (Stokes)) showed AKR1B10 inhibitory activity. To identify the active compounds from R. verniciflua responsible for AKR1B10 inhibition, nine compounds were isolated via bioactivity-guided isolation and tested for their effects against recombinant human AKR1B10 (rhAKR1B10). Results showed that butein, isolated from the ethyl acetate fraction, was most able to inhibit rhAKR1B10. The inhibitory rate of butein against rhAKR1B10 was 42.86% at 1 μM with an IC50 value of 1.47 μM, and enzyme kinetic analysis revealed its inhibition mode to be uncompetitive. [BMB reports 2010; 43(4): 268-272]

show abstract

“…The recombinant CBR1, 21) aldo-keto reductase (AKR) 1B10, 24) AKR1C1, 25) AKR1C2 26) and AKR1C3 27) were expressed from expression plasmids harboring their cDNAs and purified to homogeneity as described previously. The IC 50 (concentration required for 50% inhibition) value for QUE was determined in the NADPH-linked reduction using 0.1 mM isatin (for CBR1) 12) and 0.2 mM pyridine-3-aldehyde (for AKR1B10) 24) as the substrates, and the values with AKR1C1, AKR1C2 and AKR1C3 were estimated in nicotinamide adenine dinucleotide phosphate-linked oxidation of (S)-(+)-1,2,3,4-tetrahydro-1-naphthol as described. 28) Quantitation of DOXol Enzymatic reduction of DOX was conducted in a 10 mL system composed of 0.1 M potassium phosphate, pH 7.4, 0.4 mM NADPH, 10 µM DOX, and CBR1.…”

Section: Methodsmentioning

confidence: 99%

Up-Regulation of Carbonyl Reductase 1 Renders Development of Doxorubicin Resistance in Human Gastrointestinal Cancers

Matsunaga

Kezuka

Morikawa

et al. 2015

Biological & Pharmaceutical Bulletin

Self Cite

View full text Add to dashboard Cite

Doxorubicin (DOX) is widely used for the treatment of a wide range of cancers such as breast and lung cancers, and malignant lymphomas, but is generally less efficacious in gastrointestinal cancers. The most accepted explanation for the DOX refractoriness is its resistance development. Here, we established DOX-resistant phenotypes of human gastric MKN45 and colon LoVo cells by continuous exposure to incremental concentrations of the drug. While the parental MKN45 and LoVo cells expressed carbonyl reductase 1 (CBR1) highly and moderately, respectively, the gain of DOX resistance further elevated the CBR1 expression. Additionally, the DOX-elicited cytotoxicity was lowered by overexpression of CBR1 and inversely strengthened by knockdown of the enzyme using small interfering RNA or pretreating with the specific inhibitor quercetin, which also reduced the DOX refractoriness of the two resistant cells. These suggest that CBR1 is a key enzyme responsible for the DOX resistance of gastrointestinal cancer cells and that its inhibitor is useful in the adjuvant therapy. Although CBR1 is known to metabolize DOX to a less toxic anticancer metabolite doxorubicinol, its overexpression in the parental cells hardly show significant reductase activity toward low concentration of DOX. In contrast, the overexpression of CBR1 increased the reductase activity toward an oxidative stress-derived cytotoxic aldehyde 4-oxo-2-nonenal. The sensitivity of the DOX-resistant cells to 4-oxo-2-nonenal was lower than that of the parental cells, and the resistance-elicited hyposensitivity was almost completely ameliorated by addition of the CBR1 inhibitor. Thus, CBR1 may promote development of DOX resistance through detoxification of cytotoxic aldehydes, rather than the drug's metabolism.Key words carbonyl reductase 1; doxorubicin; drug resistance; gastrointestinal cancer cell; quercetin An anthracycline-based antibiotic doxorubicin (DOX) is widely utilized for the treatment of patients not only with solid tumors formed in many organs including breast, lung and stomach, but also with malignant lymphomas. 1) One of the major anticancer actions of DOX is intercalation into the double-stranded DNA and the resultant inhibition of DNA/RNA polymerases.1) In addition, treatment with the drug is known to form the tripartite complex with DNA and topoisomerase-II, ultimately blocking the transcription and replication of DNA. Besides the events essential for protein biosynthesis and cell proliferation, the free radical formation is proposed as another cytolethal mechanism triggered by DOX.1-3) Cellular reductases such as cytochrome P450 reductase 4) and xanthine oxidase 5) catalyze the one-electron reduction of the p-quinone structure in the anthraquinone ring of DOX into a semiquinone radical intermediate, which in turn reacts with molecular oxygen to yield superoxide anion radical. The radical is further converted into a more potent oxidizing agent hydroxyl radical, and thereby oxidatively modifies intracellular components such as nucleic acids, lipids an...

show abstract

Kinetic studies of AKR1B10, human aldose reductase-like protein: Endogenous substrates and inhibition by steroids

Cited by 94 publications

References 54 publications

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Rat Aldose Reductase-Like Protein (AKR1B14) Efficiently Reduces the Lipid Peroxidation Product 4-Oxo-2-nonenal

Inhibitory effects of polyphenols isolated from Rhus verniciflua on Aldo-keto reductase family 1 B10

Up-Regulation of Carbonyl Reductase 1 Renders Development of Doxorubicin Resistance in Human Gastrointestinal Cancers

Contact Info

Product

Resources

About