Evidence for the presence of a prostaglandin E2-9-keto reductase in rat organs

Leslie, Catherine Amoroso; Levine, Lawrence

doi:10.1016/0006-291x(73)90996-0

Cited by 101 publications

(21 citation statements)

References 5 publications

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“…The radioactive prostaglandin used had the tritium label in the 913-position. A prostaglandin 9-keto reductase has been found in rat tissues (24) leading to small losses (10%) of3H from [91-3H] prostaglandin F2, when injected into rats (25). In monkeys (26) and in humans (3), however, the label seems to be stable and thus suitable for metabolic studies.…”

Section: Discussionmentioning

confidence: 99%

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Diczfalusy¹,

Kase²,

Alexson³

et al. 1991

J. Clin. Invest.

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We have recently shown in vitro that the peroxisomal fraction of a rat liver homogenate has the highest capacity to (-oxidize prostaglandins. In order to evaluate the relative importance of peroxisomes for this conversion also in vivo, we administered [Hjprostaglandin F2. to an infant suffering from Zellweger syndrome, a congenital disorder characterized by the absence of intact peroxisomes. As a control, labeled compound was administered to two healthy volunteers. Urine was collected, fractionated on a SEP-PAK Cl3 cartridge, and subjected to reversed-phase high-performance liquid chromatography. The Zellweger patient was found to excrete prostaglandin metabolites considerably less polar than those of the control subjects. The major urinary metabolite in the control subjects was practically absent in the urine from the Zellweger patient. The major urinary prostaglandin F2. metabolite from the Zellweger patient was identified as an w-oxidized C"0-prostaglandin, 9,11-dihydroxy-15-oxoprost-5-ene-1,20-dioic acid. The major urinary prostaglandin Fu, metabolite from the control subjects had chromatographic properties of a tetranor (C16) prostaglandin, in accordance with earlier published data. The present results, in combination with our previous in vitro data, indicate that peroxisomal (i-oxidation is of major importance for in vivo chain shortening of prostaglandins. (J. Clin. Invest. 1991. 88:978-984.)

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Section: Discussionmentioning

confidence: 99%

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Diczfalusy¹,

Kase²,

Alexson³

et al. 1991

J. Clin. Invest.

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“…PGE 2 and PGF 2␣ play an important role in the tubular reabsorption of salt and water as well as in the control of renal vascular resistance and the maintenance of glomerular hemodynamics. PGE 2 is known to be converted enzymatically to PGF 2␣ (Leslie and Levine, 1973;Terragno et al, 1976), and this conversion is enhanced in pathophysiological settings including sodium depletion (Siragy and Carey, 1997). Therapeutically, since both PGE 2 and PGF 2␣ have potent oxytoxic actions, the synthetic preparations of these compounds have been used to terminate pregnancy and to facilitate labor (Foegh and Ramwell, 2001).…”

mentioning

confidence: 99%

Human Organic Anion Transporters and Human Organic Cation Transporters Mediate Renal Transport of Prostaglandins

Kimura

Takeda²,

Narikawa³

et al. 2002

J Pharmacol Exp Ther

166

108

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Prostaglandin E 2 (PGE 2 ) and prostaglandin F 2␣ (PGF 2␣ ) have been used for the induction of labor and the termination of pregnancy. Renal excretion is shown to be an important pathway for the elimination of PGE 2 and PGF 2␣ . The purpose of this study was to elucidate the molecular mechanism of renal PGE 2 and PGF 2␣ transport using cells stably expressing human organic anion transporter (hOAT) 1, hOAT2, hOAT3, and hOAT4, and human organic cation transporter (hOCT) 1 and hOCT2. A time-and dose-dependent increase in PGE 2 and PGF 2␣ uptake was observed in cells expressing hOAT1, hOAT2, hOAT3, hOAT4, hOCT1, and hOCT2. The K m values of PGE 2 uptake by hOAT1, hOAT2, hOAT3, hOAT4, hOCT1, and hOCT2 were 970, 713, 345, 154, 657, and 28.9 nM, respectively, whereas those of PGF 2␣ uptake by hOAT1, hOAT3, hOAT4, hOCT1, and hOCT2 were 575, 1092, 692, 477, and 334 nM, respectively. PGE 2 and PGF 2␣ significantly inhibited organic anion uptake by hOATs and organic cation uptake by hOCTs. In conclusion, considering the localization of these transporters, the results suggest that PGE 2 and PGF 2␣ transport in the basolateral membrane of the proximal tubule is mediated by multiple pathways including hOAT1, hOAT2, hOAT3, and hOCT2, whereas that in the apical side is mediated by hOAT4.

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“…This observation implies that the ovary has the potential for intrinsic control of its luteal function. Three different pathways have been postulated for the biosynthesis of PGF,,,: (a) 9,11 -endoperoxide reduction of PGH, [12]; (b) 1 I-ketoreduction of PGD, [13]; (c) 9-ketoreduction of PGE, [14]. The enzyme prostaglandin-E, 9-reductase (PGE, 9-reductase) has been identified in various species and tissues, differing in substrate and cofactor specificity [15][16][17][18].…”

Section: Schlegel Et Al [I 11mentioning

confidence: 99%

Prostaglandin‐E₂ 9‐Reductase from Corpus Luteum of Pseudopregnant Rabbit is a Member of the Aldo‐Keto Reductase Superfamily Featuring 20α‐Hydroxysteroid Dehydrogenase Activity

Wintergalen

Thole²,

Galla

et al. 1995

European Journal of Biochemistry

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The prostaglandin-E, 9-reductase (PGE, 9-reductase) activity in the corpus luteum of rabbits corresponds to a cytosolic, NADPH-dependent enzyme with a molecular mass of 36 kDa. This enzyme was purified from corpora lutea on day 12 of pseudopregnancy with a 266-fold enrichment. The main purification step was affinity chromatography using Red Sepharose CL-6B. The efficiency of this column was improved by elution with 1 mM NADH prior to elution of the active fractions with 1 mM NADPH.Amino acid sequence data demonstrate that the rabbit luteal PGE, 9-reductase has to be classified as a member of the aldo-keto reductase superfamily. The enzyme revealed a wide substrate specificity comprising the reduction of aldehydes, ketones, and quinones. Apparent kinetic constants were determined using methylglyoxal, DL-glyceraldehyde, and 9,lO-phenanthrenquinone as substrates. The fully purified enzyme showed two catalytic activities of particular interest: PGE, 9-reductase and 20a-hydroxysteroid dehydrogenase (20a-HSD) activities. The competitive inhibition of 20a-HSD activity by PGE, indicates that progesterone and PGE, are substrates for the same enzyme. From these results, we conclude that prostaglandin and steroid metabolism are tightly linked to each other. For this reason the aldo-keto reductase could be a key enzyme in the cascade of events leading to the regression of the corpus luteum in the rabbit.

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Evidence for the presence of a prostaglandin E2-9-keto reductase in rat organs

Cited by 101 publications

References 5 publications

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Human Organic Anion Transporters and Human Organic Cation Transporters Mediate Renal Transport of Prostaglandins

Prostaglandin‐E₂ 9‐Reductase from Corpus Luteum of Pseudopregnant Rabbit is a Member of the Aldo‐Keto Reductase Superfamily Featuring 20α‐Hydroxysteroid Dehydrogenase Activity

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Evidence for the presence of a prostaglandin E2-9-keto reductase in rat organs

Cited by 101 publications

References 5 publications

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Metabolism of prostaglandin F2 alpha in Zellweger syndrome. Peroxisomal beta-oxidation is a major importance for in vivo degradation of prostaglandins in humans.

Human Organic Anion Transporters and Human Organic Cation Transporters Mediate Renal Transport of Prostaglandins

Prostaglandin‐E2 9‐Reductase from Corpus Luteum of Pseudopregnant Rabbit is a Member of the Aldo‐Keto Reductase Superfamily Featuring 20α‐Hydroxysteroid Dehydrogenase Activity

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Prostaglandin‐E₂ 9‐Reductase from Corpus Luteum of Pseudopregnant Rabbit is a Member of the Aldo‐Keto Reductase Superfamily Featuring 20α‐Hydroxysteroid Dehydrogenase Activity