Regulation of the Aldo-Keto Reductase Gene akr1b7 by the Nuclear Oxysterol Receptor LXRα (Liver X Receptor-α) in the Mouse Intestine: Putative Role of LXRs in Lipid Detoxification Processes

Volle, David H.; Repa, Joyce J.; Mazur, Andrzej; Cummins, Carolyn L.; Val, Pierre; Henry-Berger, Joëlle; Caira, Françoise; Veyssière, G.; Mangelsdorf, David J.; Lobaccaro, Jean Marc

doi:10.1210/me.2003-0338

Cited by 46 publications

(47 citation statements)

References 40 publications

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“…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.…”

mentioning

confidence: 96%

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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mentioning

confidence: 96%

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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“…Blots were incubated at room temperature with the primary antibody for 4 h (dilution 1/3000). The antibody against maize (m)LXR (Volle et al 2004) recognizes the N-terminal domain of the LXR receptor. An anti-rabbit IgG labelled with horseradish peroxidase was used as secondary antibody (dilution 1/10 000).…”

Section: Sds-page and Western Blot Analysesmentioning

confidence: 99%

“…This showed that the LXR receptor was expressed throughout the epididymis at a level comparable to that of the liver while the LXR receptor appeared to be less represented in the epididymis than in the liver, and also slightly less represented in the cauda than in the caput epididymidis. Using a purified polyclonal antibody generated in house for the mouse LXR protein (Volle et al 2004), we carried out a western blot analysis of mouse epididymis protein extracts. The Western blot analysis presented in Fig.…”

Section: Lxr Receptors Are Differentially Expressed In the Mouse Epidmentioning

confidence: 99%

“…To determine whether caput-expressed genes (such as GPX5 or PEA3) could be direct LXRs target genes, we first carried out a computer-assisted search to screen for the presence of consensual LXR response elements (LXRE) of the type 5 -DGGTYAyynnVGKKCA-3 within their regulatory gene sequences (Volle et al 2004). One highly degenerate putative LXR-binding site was found in the distal GPX5 5 -flanking promoter region (Fig.…”

Section: Are Caput-expressed Genes Targets For Lxrs?mentioning

confidence: 99%

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Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymidis structure and functions

Frenoux¹,

Vernet²,

Volle³

et al. 2004

Journal of Molecular Endocrinology

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In this study we looked at the epididymides and spermatozoa of mice knocked-out for nuclear oxysterol receptors (LXR). We have shown that LXR-deficient mice exhibited upon ageing a severe disruption of their caput epididymides associated with abnormal accumulation of neutral lipids. The epididymis defaults were correlated with sperm head fragility and infertility. In agreement with the observed caput defect in transgenic animals in which both LXR and LXR isoforms were disrupted, we have shown here that both receptors are expressed in caput and cauda epididymides regions. LXR was predominantly expressed throughout the mouse epididymis while the expression of LXR was weaker. In addition, the expression of selected genes that can be considered as markers of adult epididymis function was monitored via Northern blots in the different single and double LXR-deficient backgrounds. Altogether, the data presented here suggest that LXR receptors are important actors in epididymis function.

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“…Therefore, a potential physiological role for AKR1B7 in the control of 4-HNE levels may have effects in a far more subtle manner than expected, leading to diverse effects on cellular physiology. Recently, an association of AKR1B7 protein with the intestinal nuclear receptor liver X receptor (LXR), acting as sterol sensor (Repa & Mangelsdorf 2002, Volle et al 2004, has been reported. These interactions and the multiple functions of adrenal glucocorticoids in inflammatory, energy, and stress reactions are starting points for future experiments which may reveal a potential role of AKR1B7 protein in non-reproductive tissues.…”

mentioning

confidence: 99%

AKR1B7 (mouse vas deferens protein) is dispensable for mouse development and reproductive success

Baumann¹,

Davies²,

Peters³

et al. 2007

Reproduction

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AKR1B7 (aldo-keto reductase family 1, member 7; also known as mouse vas deferens protein) is a member of the AKR superfamily, and has been suggested to play a role in detoxifying processes on account of its preferred substrates, 4-hydroxynonenal and isocaproaldehyde. High levels of protein expression were found in the vas deferens and the adrenal gland, where sustained expression is dependent on androgen or ACTH respectively. Recently, a remarkable induction of AKR1B7 expression has been reported in the ovary following exogenous injections of LH. In the present study, we confirm this regulation physiologically during the estrous cycle, observing Akr1b7 expression to be restricted to the theca and stromal cells of the proestrus ovary. To further investigate the role of this detoxifying enzyme in both male and female reproduction, we generated knockout mice deficient in AKR1B7. Although AKR1B7 expression in the vas deferens is considerable and tightly regulated in the ovary of wild-type animals, homozygous mutant animals were found to be viable and no reproductive phenotype was observed. Ovarian follicle maturation and spermatozoa parameters remained normal in the absence of this protein. The determination of serum progesterone revealed an increase in hormone concentration in metestrus, while progesterone was found to be decreased in the estrus phase of the cycle in knockout females.

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Regulation of the Aldo-Keto Reductase Gene akr1b7 by the Nuclear Oxysterol Receptor LXRα (Liver X Receptor-α) in the Mouse Intestine: Putative Role of LXRs in Lipid Detoxification Processes

Cited by 46 publications

References 40 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

Nuclear oxysterol receptors, LXRs, are involved in the maintenance of mouse caput epididymidis structure and functions

AKR1B7 (mouse vas deferens protein) is dispensable for mouse development and reproductive success

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