Prostaglandin catabolizing enzymes

Tai, Hsin‐Hsiung; Ensor, Mark; Tang, Min; Zhou, Hongyu; Yan, Fengxiang

doi:10.1016/s0090-6980(02)00050-3

Cited by 282 publications

(215 citation statements)

References 68 publications

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“…In vivo, PGE 2 is rapidly transformed by a non-enzymatic dehydration into PGA 2 or is metabolized into an inactive form (i.e., 15-keto PGE 2 ) by 15-hydroxy-prostaglandin dehydrogenase. 12 As shown in Figure 1a, the microinjection into an established glioma cell line (U251) of PGA 2 and 15-keto PGE 2 induced cell death, as efficiently as PGE 2 , whereas the microinjection of U46619 (the non-metabolic version of PGH 2 , the precursor of PGE 2 ), or that of the closely related molecule latanoprost lactone diol did not affect cell viability. These results suggest that a 'non-active' physiological form of PGE 2 (i.e., 15-keto PGE 2 ) is still capable of activating apoptosis but not its precursor (i.e., PGH 2 ).…”

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confidence: 90%

Prostaglandins antagonistically control Bax activation during apoptosis

et al. 2010

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The Bax protein (Bcl-2-associated X protein) is pivotal for the apoptotic process. Bax, which resides in an inactive form in the cytosol of healthy cells, is activated during the early stages of apoptosis and becomes associated with mitochondria through poorly understood mechanisms. In this study, we show that a family of bioactive lipids, namely prostaglandins, regulates Bax-dependent apoptosis. The prostaglandin E 2 (PGE 2 ) or its derivative PGA 2 binds to Bax, induces its change of conformation, and thereby triggers apoptosis. A cysteine present in the loop between the two transmembrane a-helices of Bax, Cys126 is critical for its activation. PGD 2 inhibits PGE 2 binding to Bax and PGE 2 -induced apoptosis, as well as cell death induced by staurosporine and UV-B in various cell lines. This result is consistent with the fact that apoptosis is accompanied during these treatments by an increase in PGE 2 . This process is distinct, yet cooperative, from that involving the BH3-only protein Bid. Our results establish that the PGE 2 /PGD 2 balance is involved in a new early mechanism of control in the activation of Bax during apoptosis. Cell Death and Differentiation (2011) 18, 528-537; doi:10.1038/cdd.2010.128; published online 22 October 2010Members of the Bcl-2 (Bcl-2-associated X protein) family of proteins determine both the initiation and the execution of mitochondrial outer membrane permeabilization (MOMP) and the subsequent apoptosis. These proteins share a similar solution structure, and are subdivided into two groups: antiapoptotic proteins (e.g., Bcl-2, Bcl-Xl, Bcl-W and Mcl-1) and proapoptotic proteins, which control apoptosis through complex interaction with each other. Proapoptotic proteins are further subdivided into multidomain proteins (namely, Bax, Bak and Bok) and BH3-only proteins (e.g., Bim, Bad, Bid, Puma or Noxa) whose homology with Bcl-2 is limited to the BH3 domain. BH3-only proteins function as upstream sensors that selectively respond to specific signals and promote the proapoptotic function of Bax and/or Bak. Both in vivo and in vitro experiments have proved that the conformation of monomeric Bax/Bak change upon induction of apoptosis, leading to their oligomerization in the mitochondrial membrane and MOMP. [1][2][3] How Bax and Bak are activated is a matter of debate. 2,4 A widely accepted model proposes that some BH3-only proteins called 'activators' (tBid, Bim and Puma) induce the Bax/Bak apoptotic conformational change through transient physical interaction in a 'hit and run' manner. Another group named 'enabler' (also called derepressor or sensitizer) can release Bax and Bak from antiapoptotic proteins, which in turn trigger MOMP. [1][2][3] The existence of a direct interaction of Bax/Bak with BH3-only proteins has been challenged, suggesting the existence of alternative mechanisms responsible for the activation of Bax or Bak. A change in pH or temperature has also been shown to facilitate the transition between the inactive and active states of Bax, supporting a role for nonprotein...

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Prostaglandins antagonistically control Bax activation during apoptosis

et al. 2010

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“…The primary inactivating step comprises the oxidation of the 15-hydroxyl group to a 15-keto group by HPGD. Further inactivation is performed by the reduction at D13 double bond by a D13-15-keto PG reductase to the stable metabolites 13,14-dihydro-15-keto PG referred to as PGFM (Tai et al 2002). PGI 2 is chemically unstable, the stable breakdown product 6-keto PGF 1a , however, reflects PGI 2 concentrations directly.…”

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confidence: 99%

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Ulbrich¹,

Schülke²,

Groebner³

et al. 2009

Reproduction

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Prostaglandins (PGs) are important regulators of reproductive processes including early embryonic development. We analyzed the most relevant PG in bovine uteri at different preimplantation pregnancy stages when compared with non-pregnant controls. Additionally, endometrium and trophoblast tissues were examined regarding specific enzymes and receptors involved in PG generation and function. Simmental heifers were artificially inseminated or received seminal plasma only. At days 12, 15, or 18, post-estrus uteri were flushed for PG determination by liquid chromatography-tandem mass spectrometry. Endometrium and trophoblast tissues were sampled for RNA extraction and quantitative real-time PCR analysis. At all days and points of time examined, the concentration of 6-keto PGF 1a (stable metabolite of PGI 2 ) was predominant followed by PGF 2a OPGE 2 OPGD 2 zTXB 2 (stable metabolite of TXA 2 ). At days 15 and 18, PG increased from overall low levels at day 12, with a much more pronounced increase during pregnancy. The PGF 2a /PGE 2 ratio was not influenced by status. The highest PG concentration was measured at day 15 with 6-keto PGF 1a (6.4 ng/ml) followed by PGF 2a (1.1 ng/ml) and PGE 2 (0.3 ng/ml). Minor changes in endometrial PG biosynthesis enzymes occurred due to pregnancy. Trophoblasts revealed high transcript abundance of general and specific PG synthases contributing to uterine PG. As PGI 2 and PGF 2a receptors were abundantly expressed by the trophoblast, abundant amounts of PGI 2 and PGF 2a in the uterine lumen point towards an essential role of PG for the developing embryo. High amounts of PG other than PGE 2 in the preimplantation uterus may be essential rather than detrimental for successful reproduction.

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“…However, little is known about whether the catabolism of PGE 2 is associated with modulation of PPAR␥ activity (19). PGE 2 , a short-lived mediator, is inactivated via an oxidation reaction catalyzed by NAD ϩ -dependent 15-hydroxyprostaglandin dehydrogenase (PGDH), which generates 15-keto-PGE 2 , which is, in turn, further catabolized by a reaction catalyzed by NADPH/NADH-dependent 15-oxoprostaglandin-⌬ 13 -reductase (PGR) (20). It has been shown that adipose tissue possesses high activity of both PGDH and PGR, indicating that PGE 2 catabolism is highly active in adipocytes (21).…”

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Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E2 Catabolism in Regulation of Peroxisome Proliferator-activated Receptor γ Activation

Chou

Chuang

Chou

et al. 2007

Journal of Biological Chemistry

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This report identifies a novel gene encoding 15-oxoprostaglandin-⌬ 13 -reductase (PGR-2), which catalyzes the reaction converting 15-keto-PGE 2 to 13,14-dihydro-15-keto-PGE 2 . The expression of PGR-2 is up-regulated in the late phase of 3T3-L1 adipocyte differentiation and predominantly distributed in adipose tissue. Overexpression of PGR-2 in cells decreases peroxisome proliferator-activated receptor ␥ (PPAR␥)-dependent transcription and prohibits 3T3-L1 adipocyte differentiation without affecting expression of PPAR␥. Interestingly, we found that 15-keto-PGE 2 can act as a ligand of PPAR␥ to increase coactivator recruitment, thus activating PPAR␥-mediated transcription and enhancing adipogenesis of 3T3-L1 cells. Overexpression of 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation reaction of PGE 2 to form 15-keto-PGE 2, significantly increased PPAR␥-mediated transcription in a PGE 2 -dependent manner. Reciprocally, overexpression of wild-type PGR-2, but not the catalytically defective mutant, abolished the effect of 15-keto-PGE 2 on PPAR␥ activation. These results demonstrate a novel link between catabolism of PGE 2 and regulation of ligand-induced PPAR␥ activation.

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Prostaglandin catabolizing enzymes

Cited by 282 publications

References 68 publications

Prostaglandins antagonistically control Bax activation during apoptosis

Prostaglandins antagonistically control Bax activation during apoptosis

Quantitative characterization of prostaglandins in the uterus of early pregnant cattle

Identification of a Novel Prostaglandin Reductase Reveals the Involvement of Prostaglandin E2 Catabolism in Regulation of Peroxisome Proliferator-activated Receptor γ Activation

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