Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Lambert-Langlais, Sarah; Pointud, Jean-Christophe; Lefrançois‐Martinez, Anne‐Marie; Volat, Fanny; Manin, M.; François, Clément; Val, Pierre; Sahut‐Barnola, Isabelle; Ragazzon, Bruno; Louiset, Estelle; Delarue, Catherine; Lefebvre, Henri; Urade, Yoshihiro; Martinez, Antoine

doi:10.1371/journal.pone.0007309

Cited by 26 publications

(41 citation statements)

References 53 publications

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“…However, there is no report on the detailed properties of AKR1B14, except for its role as a PGF 2a synthase in rat adrenal cells. 23) Recently, we have established the bacterial overexpression system of recombinant AKR1B14, which provided high yield of the enzyme and subsequently lead to successful crystallisation attempts. 24) In this study, we examined the substrate specificity of recombinant AKR1B14 in both the reduction and oxidation directions in order to elucidate the enzyme function related to the hepatic expression induced by oxidative stress.…”

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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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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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“…By using their purified recombinant proteins, we recently demonstrated that several members of the AKR1B family, such as human AKR1B1, mouse AKR1B3, and bovine AKR1B5, have PGFS activity higher than that of AKR1C3 (30). Among those members of the AKR1B family, AKR1B7 was demonstrated by Lambert-Langlais et al (31) to be involved in the production of PGF 2␣ in adrenal glands for inhibition of glucocorticoid secretion. Tirard et al (32) previously reported that overexpression of Akr1b7 suppressed lipid accumulation in transfected 3T3-L1 cells.…”

Section: Discussionmentioning

confidence: 99%

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Fujimori

Ueno

Nagata

et al. 2010

Journal of Biological Chemistry

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Prostaglandin (PG) F 2␣ suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferatoractivated receptor ␥. However, PGF 2␣ synthase (PGFS) in adipocytes remains to be identified. Here, we studied the expression of members of the aldo-keto reductase (AKR) 1B family acting as PGFS during adipogenesis of mouse 3T3-L1 cells. AKR1B3 mRNA was expressed in preadipocytes, and its level increased about 4-fold at day 1 after initiation of adipocyte differentiation, and then quickly decreased the following day to a level lower than that in the preadipocytes. In contrast, the mRNA levels of Akr1b8 and 1b10 were clearly lower than that level of Akr1b3 in preadipocytes and remained unchanged during adipogenesis. The transient increase in Akr1b3 during adipogenesis was also observed by Western blot analysis. The mRNA for the FP receptor, which is selective for PGF 2␣ , was also expressed in preadipocytes. Its level increased about 2-fold within 1 h after the initiation of adipocyte differentiation and was maintained at almost the same level throughout adipocyte differentiation. The small interfering RNA for Akr1b3, but not for Akr1b8 or 1b10, suppressed PGF 2␣ production and enhanced the expression of adipogenic genes such as peroxisome proliferator-activated receptor ␥, fatty acid-binding protein 4 (aP2), and stearoylCoA desaturase. Moreover, an FP receptor agonist, Fluprostenol, suppressed the expression of those adipogenic genes in 3T3-L1 cells; whereas an FP receptor antagonist, AL-8810, efficiently inhibited the suppression of adipogenesis caused by the endogenous PGF 2␣ . These results indicate that AKR1B3 acts as the PGFS in adipocytes and that AKR1B3-produced PGF 2␣ suppressed adipocyte differentiation by acting through FP receptors.

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“…Further, Akr1b7 participates in steroid synthesis in the adrenal gland, where renin is also expressed in fetal life. 28 Most recently, Akr1b7 has been shown to be crucial in the synthesis of prostaglandins, 29 which, in turn, are known to regulate renin synthesis and release, 1 suggesting that AKR1B7 may regulate renin release by an intracrine mechanism. Further studies will be necessary to determine the role of Akr1b7 in renin cells.…”

Section: Novel Features Of the Present Work Include The Extensive Commentioning

confidence: 99%

Genes that Confer the Identity of the Renin Cell

Brunskill

Sequeira-Lόpez

Pentz

et al. 2011

Journal of the American Society of Nephrology

111

162

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Renin-expressing cells modulate BP, fluid-electrolyte homeostasis, and kidney development, but remarkably little is known regarding the genetic regulatory network that governs the identity of these cells.Here we compared the gene expression profiles of renin cells with most cells in the kidney at various stages of development as well as after a physiologic challenge known to induce the transformation of arteriolar smooth muscle cells into renin-expressing cells. At all stages, renin cells expressed a distinct set of genes characteristic of the renin phenotype, which was vastly different from other cell types in the kidney. For example, cells programmed to exhibit the renin phenotype expressed Akr1b7, and maturing cells expressed angiogenic factors necessary for the development of the kidney vasculature and RGS (regulator of G-protein signaling) genes, suggesting a potential relationship between renin cells and pericytes. Contrary to the plasticity of arteriolar smooth muscle cells upstream from the glomerulus, which can transiently acquire the embryonic phenotype in the adult under physiologic stress, the adult juxtaglomerular cell always possessed characteristics of both smooth muscle and renin cells. Taken together, these results identify the gene expression profile of renin-expressing cells at various stages of maturity, and suggest that juxtaglomerular cells maintain properties of both smooth muscle and renin-expressing cells, likely to allow the rapid control of body fluids and BP through both contractile and endocrine functions.

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Aldo Keto Reductase 1B7 and Prostaglandin F2α Are Regulators of Adrenal Endocrine Functions

Cited by 26 publications

References 53 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

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Genes that Confer the Identity of the Renin Cell

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