Recent advances in studies of 15-PGDH as a key enzyme for the degradation of prostaglandins

Sun, Chaofen; Zhou, Zuoqiong; Yang, Dong Kwon; Chen, Zhanglin; Zhou, Yunyi; Wei, Wen Jun; Chen, Feng; Zheng, Lingjie; Peng, Xiyang; Tang, Cui

doi:10.1016/j.intimp.2021.108176

Cited by 10 publications

(9 citation statements)

References 139 publications

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“…It is mainly known as an inflammation mediator and exerts its action via the interaction with four different receptors, E-type prostanoid receptors 1–4 (EP1-4), that are widely expressed in platelets and VSMCs [ 10 , 144 , 145 ]. PGE2 is synthesized in many cell types, including endothelial cells, platelets, macrophages, and fibroblasts, and is rapidly inactivated into 15-keto-PGE2 by 15-hydroxyprostaglandin dehydrogenase (15-PGDH or prostaglandin dehydrogenase 1) [ 146 ]. It is involved in many processes and in the pathogenesis of several diseases.…”

Section: Prostanoidsmentioning

confidence: 99%

The Link between Prostanoids and Cardiovascular Diseases

Beccacece

Abondio

Bini

et al. 2023

IJMS

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Cardiovascular diseases are the leading cause of global deaths, and many risk factors contribute to their pathogenesis. In this context, prostanoids, which derive from arachidonic acid, have attracted attention for their involvement in cardiovascular homeostasis and inflammatory processes. Prostanoids are the target of several drugs, but it has been shown that some of them increase the risk of thrombosis. Overall, many studies have shown that prostanoids are tightly associated with cardiovascular diseases and that several polymorphisms in genes involved in their synthesis and function increase the risk of developing these pathologies. In this review, we focus on molecular mechanisms linking prostanoids to cardiovascular diseases and we provide an overview of genetic polymorphisms that increase the risk for cardiovascular disease.

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Section: Prostanoidsmentioning

confidence: 99%

The Link between Prostanoids and Cardiovascular Diseases

Beccacece

Abondio

Bini

et al. 2023

IJMS

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“…Also the leukotriene/prostaglandin pathway was deemed as downregulated in active IBD in our data set, suggesting reduced prostaglandin and leukotriene signaling. However, in depth characterization of the pathways’ genes that contributed to this somewhat unexpected finding, showed that HPGD and EPHX2 , both enzymes crucial for breaking down the inflammatory mediators prostaglandin and epoxyeicosatrienoic acids, were reduced, 34 , 35 while the enzymes ALOX5, ALOX15 and ALOX5AP mediating the transition from arachidonic acid to leukotrienes were increased. 36 Hence, this supports a role for increased activity of leukotriene and prostaglandin mediators in maintaining inflammation in patients with active disease.…”

Section: Discussionmentioning

confidence: 99%

“…Clinical and Experimental Gastroenterology 2022:15 down the inflammatory mediators prostaglandin and epoxyeicosatrienoic acids, were reduced, 34,35 while the enzymes ALOX5, ALOX15 and ALOX5AP mediating the transition from arachidonic acid to leukotrienes were increased. 36 Hence, this supports a role for increased activity of leukotriene and prostaglandin mediators in maintaining inflammation in patients with active disease.…”

Section: Dovepressmentioning

confidence: 99%

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis

Holst¹,

Halfvarson²,

Carlson³

et al. 2022

CEG

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Background: Improved mucosal immune profiling in active and quiescent colonic inflammatory bowel disease (IBD) is needed to develop therapeutic options for treating and preventing flares. This study therefore aimed to provide a comprehensive mucosal characterization with emphasis on immunological host response of patients with active ulcerative colitis (UC active), UC during remission (UC remission) and active colonic Crohn's disease (CD active). Methods: Colonic biopsies from 47 study subjects were collected for gene expression and pathway analyses using the NanoString host-response panel, including 776 genes and 56 immune-related pathways. Results: The majority of mucosal gene expression and signaling pathway scores were increased in active IBD (n=27) compared to healthy subjects (n=10). However, both active IBD and UC remission (n=10) demonstrated decreased gene expression and signaling pathway scores related to autophagy, alpha kinase-1 and IL-17 signaling pathways compared to healthy subjects. Further, UC remission was characterized by decreased scores of several signaling pathways linked to homeostasis along with increased mononuclear cell migration pathway score as compared to healthy subjects. No major differences in the colonic mucosal gene expression between CD active (n=7) and UC (n=20) active were observed. Conclusion:This study indicates that autophagy, alpha kinase-1 and IL-17 signaling pathways are persistently downregulated in UC irrespective of disease activity. Further, UC patients in remission present a unique mucosal environment, potentially preventing patients from reaching and sustaining true homeostasis. These findings may enable better comprehension of the remitting and relapsing pattern of colonic IBD and guide future treatment and prevention of flares.

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“…Their concentrations and basic characteristics are summarized in Table 1, and Supplementary Table S1 lists their molecular identity, including molecular structure, as well as possible synonym names that were used throughout the literature. Plasma: 3-12 pg/mL t 1/2 < 1min in circulation [27].…”

Section: Metabolism Of Prostanoidsmentioning

confidence: 98%

“…PGE 2 , PGD 2 , and PGF 2α have halflives in the circulation that are reported to be in the range of minutes [24,28,52] (Table 1). The ubiquitously expressed enzyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH) [27] oxidizes these three prostanoids at the hydroxyl group at C-15 and thereby renders them biologically inactive. PGI 2 and TXA 2 follow a somewhat different path with even shorter half-lives than that of the other prostanoids, which were reported to be in the range of seconds [39] (Table 1).…”

Section: Metabolism Of Prostanoidsmentioning

confidence: 99%

Prostanoid Metabolites as Biomarkers in Human Disease

Idborg

Pawelzik

2022

Metabolites

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Prostaglandins (PGD2, PGE2, PGF2α), prostacyclin (PGI2), and thromboxane A2 (TXA2) together form the prostanoid family of lipid mediators. As autacoids, these five primary prostanoids propagate intercellular signals and are involved in many physiological processes. Furthermore, alterations in their biosynthesis accompany a wide range of pathological conditions, which leads to substantially increased local levels during disease. Primary prostanoids are chemically instable and rapidly metabolized. Their metabolites are more stable, integrate the local production on a systemic level, and their analysis in various biological matrices yields valuable information under different pathological settings. Therefore, prostanoid metabolites may be used as diagnostic, predictive, or prognostic biomarkers in human disease. Although their potential as biomarkers is great and extensive research has identified major prostanoid metabolites that serve as target analytes in different biofluids, the number of studies that correlate prostanoid metabolite levels to disease outcome is still limited. We review the metabolism of primary prostanoids in humans, summarize the levels of prostanoid metabolites in healthy subjects, and highlight existing biomarker studies. Since analysis of prostanoid metabolites is challenging because of ongoing metabolism and limited half-lives, an emphasis of this review lies on the reliable measurement and interpretation of obtained levels.

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Recent advances in studies of 15-PGDH as a key enzyme for the degradation of prostaglandins

Cited by 10 publications

References 139 publications

The Link between Prostanoids and Cardiovascular Diseases

The Link between Prostanoids and Cardiovascular Diseases

Downregulated Mucosal Autophagy, Alpha Kinase-1 and IL-17 Signaling Pathways in Active and Quiescent Ulcerative Colitis

Prostanoid Metabolites as Biomarkers in Human Disease

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