Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro.

Fitzpatrick, Francis A.; Wynalda, Michael A.

doi:10.1016/s0021-9258(17)44287-6

Cited by 304 publications

(37 citation statements)

References 39 publications

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“…15‐d‐PGJ2 is a dehydration product of PGD2 and has a highly reactive cyclopentenone ring, which readily reacts with substances containing nucleophilic groups and covalently modifies proteins 27,28 . It has been reported that 15‐d‐PGJ2 exerts an anti‐inflammatory effect by binding to PPARγ 29,30 .…”

Section: Resultsmentioning

confidence: 99%

“…The drastic increase of 15‐d‐PGJ2, PGE2, and PGD2 contributed to the enrichment of AA metabolism, especially the generation of metabolites of 15‐d‐PGJ2 and PGD2. Both PGD2 and 15‐d‐PGJ2 have anti‐inflammatory effects, however, PGD2 is inherently not stable in physiologic solutions as albumin catalyzes the dehydration of PGD2 to 15‐d‐PGJ2 9,27 . Thus, 15‐d‐PGJ2 maybe a major contributor to the improved survival to sepsis upon TP5 treatment.…”

Section: Discussionmentioning

confidence: 99%

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Thymopentin improves the survival of septic mice by promoting the production of 15‐deoxy‐prostaglandin J2 and activating the PPARγ signaling pathway

et al. 2020

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Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg‐Lys‐Asp‐Val‐Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)‐induced sepsis, as shown by improved survival rate, decreased level of pro‐inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS‐stimulated macrophages by increasing the production of 15‐deoxy‐Δ12,14‐prostaglandin J2 (15‐d‐PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator‐activated receptor γ (PPARγ) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP‐induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Thymopentin improves the survival of septic mice by promoting the production of 15‐deoxy‐prostaglandin J2 and activating the PPARγ signaling pathway

et al. 2020

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“…Treatment of PGE2 and PGD2 with base induces dehydration of the hydroxyl groups at C-11 or C-9, respectively, resulting in formation of the respective enone prostanoids (21,22). Base treatment dehydrates PGE2 (lmax 205 nm) to the enone PGA2 (lmax 217 nm) ( 23) that further rearranges to the dienone PGB2 with lmax at 278 nm (Fig.…”

Section: Stability Of 5-oh-pgd2 and 5-oh-pge2mentioning

confidence: 99%

Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2 and 5-Hydroxy-PGD2

Nakashima¹,

Suzuki²,

Gordon³

et al. 2021

Preprint

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Biosynthetic crossover of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2) enzymatic activities is a productive pathway to convert arachidonic acid into unique eicosanoids. Here we show that COX-2 catalysis with 5-LOX derived 5-hydroxy-eicosatetraenoic acid yields the endoperoxide 5-hydroxy-PGH2 that spontaneously rearranges to 5-OH-PGE2 and 5-OH-PGD2, the 5-hydroxy analogs of arachidonic acid derived PGE2 and PGD2. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6E,8E,10E-enoic acid, and by SnCl2-mediated reduction to 5-OH-PGF2a. Both 5-OH-PGE2 and 5-OH-PGD2 were unstable and degraded rapidly upon treatment with weak base. The instability hampered detection in biologic samples which was overcome by in situ reduction using NaBH4 to yield the corresponding stable 5-OH-PGF2 diastereomers and enabled detection of 5-OH-PGF2a in activated primary human leukocytes. 5-OH-PGE2 and 5-OH-PGD2 were unable to activate EP and DP prostanoid receptors suggesting their bioactivity is distinct from PGE2 and PGD2.

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“…In toxicology, understanding the mechanistic interactions of organophosphates (OPs) with albumin could help in the development of new types of antidotes [29]. Among the other activities of serum albumin, one should note its prostaglandin D synthase and other activities associated with prostanoid metabolism [30][31][32]. Quite exotic activities for albumin are glucuronidase activity [33,34] and the enolase activity [35]; the latter can be used for the differential diagnostics of benign and malignant tumors.…”

Section: Enzymatic Propertiesmentioning

confidence: 99%

Serum Albumin

et al. 2020

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Being one of the most abundant proteins in human and other mammals, albumin plays a crucial role in transporting various endogenous and exogenous molecules and maintaining of colloid osmotic pressure of the blood. It is not only the passive but also the active participant of the pharmacokinetic and toxicokinetic processes possessing a number of enzymatic activities. A free thiol group of the albumin molecule determines the participation of the protein in redox reactions. Its activity is not limited to interaction with other molecules entering the blood: of great physiological importance is its interaction with the cells of blood, blood vessels and also outside the vascular bed. This entry contains data on the enzymatic, inflammatory and antioxidant properties of serum albumin.

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Albumin-catalyzed metabolism of prostaglandin D2. Identification of products formed in vitro.

Cited by 304 publications

References 39 publications

Thymopentin improves the survival of septic mice by promoting the production of 15‐deoxy‐prostaglandin J2 and activating the PPARγ signaling pathway

Thymopentin improves the survival of septic mice by promoting the production of 15‐deoxy‐prostaglandin J2 and activating the PPARγ signaling pathway

Biosynthetic Crossover of 5-Lipoxygenase and Cyclooxygenase-2 Yields 5-Hydroxy-PGE2 and 5-Hydroxy-PGD2

Serum Albumin

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