Interplay between the prostaglandin transporter OATP2A1 and prostaglandin E2-mediated cellular effects

Bujok, Krystyna; Glaeser, Hartmut; Schuh, Wolfgang; Rau, Tilman T.; Schmidt, Ingrid; Fromm, Martin F.; Mandery, Kathrin

doi:10.1016/j.cellsig.2014.11.027

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…SLCO2A1 belongs to the organic anion transporting polypeptide family and is also known as OATP2A1 and transports metabolites of the arachidonic acid cascade including PG, thromboxane, and prostacyclin. 18 Among the arachidonic metabolites, SLCO2A1 has high affinity for PGE 2 , PGE 3 , PGD 2 , and PGF 2α . 19,20 Genetic analyses revealed that CEAS is an autosomal recessive inherited disease caused by mutations in the SLCO2A1 gene; however, a functional analysis of the mutant proteins has not yet been performed.…”

Section: Discussionmentioning

confidence: 99%

“…SLCO2A1 is located on chromosome 3q21 and encodes a membrane transporter protein with a 12‐transmembrane helix. SLCO2A1 belongs to the organic anion transporting polypeptide family and is also known as OATP2A1 and transports metabolites of the arachidonic acid cascade including PG, thromboxane, and prostacyclin 18 . Among the arachidonic metabolites, SLCO2A1 has high affinity for PGE 2 , PGE 3 , PGD 2 , and PGF 2α 19,20 .…”

Section: Discussionmentioning

confidence: 99%

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Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1

Seki

Tanaka

Kimura

et al. 2022

J of Gastro and Hepatol

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Background and Aim Chronic enteropathy associated with the solute carrier organic anion transporter family member 2A1 (SLCO2A1), or CEAS, causes anemia and hypoalbuminemia in young people. Dysfunction of the SLCO2A1 transporter protein is thought to involve genetic mutation, but mutant proteins have not been functionally characterized. We examined the prostaglandin E2 (PGE2) transport ability of recombinant SLCO2A1 proteins containing 11 SLCO2A1 mutations found in CEAS patients. Methods Wild‐type and mutant SLCO2A1 proteins were forcibly expressed in Xenopus laevis oocytes, and measurements of PGE2 uptake and transport capacity were compared. The membrane protein topology and functionality of the eight SLCO2A1 mutations involving single‐nucleotide substitutions were predicted using computer analysis. Results The extent of functional disruption of the 11 SLCO2A1 mutations identified in CEAS patients was variable, with 10 mutations (421GT, 547GA, 664GA, 770GA, 830dupT, 830delT, 940 + 1GA, 1372GT, 1647GT, and 1807CT) resulting in loss or reduction of PGE2 transport, excluding 97GC. Conclusion PGE2 transport ability of recombinant SLCO2A1 in X. laevis oocytes was hindered in 10/11 SLCO2A1 mutations identified in patients with CEAS. Further studies on the relationships between the different mutations and PGE2 transport and clinical features, such as severity, are needed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1

Seki

Tanaka

Kimura

et al. 2022

J of Gastro and Hepatol

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“…Reduced SLCO2A1 expression has been associated with increasing PGE 2 levels in the tumor microenvironment and, consequently, with tumor angiogenesis in GC [ 51 ]. Moreover, colocalization of this transporter and the PGE 2 receptor EP4 has been detected in the mucosa of both normal stomach and gastric carcinoma, suggesting a role of SLCO2A1 in the PGE 2 -mediated cellular effects [ 52 ]. In the same study, by Bujok et al [ 52 ], a higher expression of the protein was found in GC tissue compared to normal tissue, but with no statistical significance.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, colocalization of this transporter and the PGE 2 receptor EP4 has been detected in the mucosa of both normal stomach and gastric carcinoma, suggesting a role of SLCO2A1 in the PGE 2 -mediated cellular effects [ 52 ]. In the same study, by Bujok et al [ 52 ], a higher expression of the protein was found in GC tissue compared to normal tissue, but with no statistical significance. Takeda et al [ 53 ] were the first to identify SLCO2A1 expression as an independent predictor of poor prognosis in patients with GC.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E2 Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population

Lopes

Pereira

Farinha

et al. 2020

IJMS

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Gastric cancer (GC) represents the third leading cause of cancer-related deaths worldwide. The levels of prostaglandin E2, a key player in the hallmarks of cancer, are mainly regulated by prostaglandin-endoperoxide synthase 2 (PTGS2) and ATP-binding cassette subfamily C member 4 (ABCC4), involved in its synthesis and exportation, respectively, and 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and solute carrier organic anion transporter family member 2A1 (SLCO2A1), responsible for its inactivation. Even though there are distinct molecular signatures across ethnic populations, most published studies focus on Asian populations. Our main aim was to explore the genetic expression of the aforementioned molecules in a Caucasian population. 94 “Normal” and 89 tumoral formalin-fixed paraffin-embedded (FFPE) samples from GC patients were used to assess the mRNA expression of PTGS2, ABCC4, hydroxyprostaglandin dehydrogenase 15-(NAD) (HPGD), SLCO2A1 by Real-Time PCR. We found an upregulation for the PTGS2 gene mean factor of 2.51 and a downregulation for the HPGD and SLCO2A1 genes (mean factor of 0.10 and 0.37, respectively) in tumorous mucosa in a gender-independent manner. In females, we observed an ABCC4 downregulation and a PTGS2 mRNA upregulation compared to males in tumoral mucosa (mean factor of 0.61 and 1.64, respectively). We reported dysregulation of the inflammation triggered PGE2 pathway in a Caucasian population with an intermediate risk for GC, which might highlight the applicability of aspirin in the treatment of GC patients.

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A Rare Cause of Blood in Stool and Anemia

Chen,

Fu,

Fan

2024

Gastroenterology

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Interplay between the prostaglandin transporter OATP2A1 and prostaglandin E2-mediated cellular effects

Cited by 4 publications

References 37 publications

Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1

Functional analysis of mutant SLCO2A1 transporters found in patients with chronic enteropathy associated with SLCO2A1

Prostaglandin E2 Pathway Is Dysregulated in Gastric Adenocarcinoma in a Caucasian Population

A Rare Cause of Blood in Stool and Anemia

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