Prostaglandin F2  Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7

Kabututu, Zakayi; Manin, M.; Pointud, Jean-Christophe; Maruyama, Toshisuke; Nagata, Nanae; Lambert, Sarah F.; Lefrançois‐Martinez, Anne‐Marie; Martinez, Antoine; Urade, Yoshihiro

doi:10.1093/jb/mvn152

Cited by 75 publications

(90 citation statements)

References 36 publications

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“…Recent works have documented the interaction of several PGs with enzymes of the AKR family (Nagata et al, 2011), and the role of AKR1B1 in PG synthesis (Kabututu et al, 2009). Therefore, we explored the effect of several PGs as potential inhibitors of AKR1B1.…”

Section: Resultsmentioning

confidence: 99%

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Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Díez-Dacal¹,

Sánchez‐Gómez

Sánchez‐Murcia

et al. 2015

Mol Pharmacol

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Aldose reductase (AKR1B1) is a critical drug target because of its involvement in diabetic complications, inflammation, and tumorigenesis. However, to date, development of clinically useful inhibitors has been largely unsuccessful. Cyclopentenone prostaglandins (cyPGs) are reactive lipid mediators that bind covalently to proteins and exert anti-inflammatory and antiproliferative effects in numerous settings. By pursuing targets for modification by cyPGs we have found that the cyPG PGA 1 binds to and inactivates AKR1B1. A PGA 1 -AKR1B1 adduct was observed, both by matrix-assisted laser desorption/ ionization time-of-flight mass spectrometry and by SDS-PAGE using biotinylated PGA 1 (PGA 1 -B). Insight into the molecular interactions between AKR1B1 and PGA 1 was advanced by molecular modeling. This anticipated the addition of PGA 1 to active site Cys298 and the potential reversibility of the adduct, which was supported experimentally. Indeed, loss of biotin label from the AKR1B1-PGA 1 -B adduct was favored by glutathione, indicating a retro-Michael reaction, which unveils new implications of cyPG-protein interaction. PGA 1 elicited only marginal inhibition of aldehyde reductase (AKR1A1), considered responsible for the severe adverse effects of many AKR1B1 inhibitors. Interestingly, other prostaglandins (PGs) inhibited the enzyme, including non-electrophilic PGE 1 and PGE 2 , currently used in clinical practice. Moreover, both PGA 1 and PGE 1 reduced the formation of sorbitol in an ex-vivo model of diabetic cataract to an extent comparable to that attained by the known AKR inhibitor epalrestat. Taken together, these results highlight the role of PGs as AKR1B1 inhibitors and the interest in PG-related molecules as leads for the development of novel pharmacological tools.

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Section: Resultsmentioning

confidence: 99%

“…AKR1B1 has also been involved in allergic inflammation and asthma Yadav et al, 2013). Moreover, AKR1B1 participates in the metabolism of certain prostaglandins (PGs), thus regulating the generation of inflammatory or vasoactive mediators (Kabututu et al, 2009;Michaud et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Díez-Dacal¹,

Sánchez‐Gómez

Sánchez‐Murcia

et al. 2015

Mol Pharmacol

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“…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.…”

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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

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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...

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“…Although it is impossible to exclude the possibility completely, it is unlikely that SIRT1-related activity mediates anti-adipogenic actions, as butein is more potent than resveratrol in terms of inhibiting adipogenesis and STAT3 activation. Other studies have shown that butein inhibits aldo-keto reductase 1B family members, resulting in less prostaglandin F2 ␣ production ( 38,39 ). However, knockdown and pharmacological inhibition of aldo-keto reductase induces adipogenesis and PPAR ␥ expression ( 40 ).…”

Section: Discussionmentioning

confidence: 98%

Butein is a novel anti-adipogenic compound

Song

Yoon

Kim

et al. 2013

Journal of Lipid Research

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Prostaglandin F2 Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7

Cited by 75 publications

References 36 publications

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

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

Butein is a novel anti-adipogenic compound

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Prostaglandin F2 Synthase Activities of Aldo-Keto Reductase 1B1, 1B3 and 1B7

Cited by 75 publications

References 36 publications

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA1 and Clinically Used Prostaglandins

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

Butein is a novel anti-adipogenic compound

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Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins

Molecular Interactions and Implications of Aldose Reductase Inhibition by PGA₁ and Clinically Used Prostaglandins