Coupling between cyclooxygenases and prostaglandin F2α synthase

Nakashima, Karin; Ueno, Noriko; Kamei, Daisuke; Tanioka, Toshihiro; Nakatani, Yoshihito; Murakami, Makoto; Kudo, Ichiro

doi:10.1016/s1388-1981(03)00092-1

Cited by 16 publications

(15 citation statements)

References 29 publications

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“…S2B) was markedly lower than that produced in 3T3-L1 cells (231 pg/ml, Fig. 2C), being consistent with the previous report that the ectopic expression of membrane-type PGFS with COX in 293 cells resulted in very low PGF 2␣ production (35). Moreover, in the heterologous expression system in 293 cells, the intracellular localization of the FLAG-tagged AKR1B3 protein did not change after an increase in the intracellular calcium level, 4 being different from that of other cytosolic terminal PG synthases such as hematopoietic PGD synthase and cytosolic PGE synthase, both of which show membrane trafficking after the increase in the intracellular calcium level (36 -38).…”

Section: Akr1b3 As Pgfs In Adipocytessupporting

confidence: 92%

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Fujimori

Ueno

Nagata

et al. 2010

Journal of Biological Chemistry

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Prostaglandin (PG) F 2␣ suppresses adipocyte differentiation by inhibiting the function of peroxisome proliferatoractivated receptor ␥. However, PGF 2␣ synthase (PGFS) in adipocytes remains to be identified. Here, we studied the expression of members of the aldo-keto reductase (AKR) 1B family acting as PGFS during adipogenesis of mouse 3T3-L1 cells. AKR1B3 mRNA was expressed in preadipocytes, and its level increased about 4-fold at day 1 after initiation of adipocyte differentiation, and then quickly decreased the following day to a level lower than that in the preadipocytes. In contrast, the mRNA levels of Akr1b8 and 1b10 were clearly lower than that level of Akr1b3 in preadipocytes and remained unchanged during adipogenesis. The transient increase in Akr1b3 during adipogenesis was also observed by Western blot analysis. The mRNA for the FP receptor, which is selective for PGF 2␣ , was also expressed in preadipocytes. Its level increased about 2-fold within 1 h after the initiation of adipocyte differentiation and was maintained at almost the same level throughout adipocyte differentiation. The small interfering RNA for Akr1b3, but not for Akr1b8 or 1b10, suppressed PGF 2␣ production and enhanced the expression of adipogenic genes such as peroxisome proliferator-activated receptor ␥, fatty acid-binding protein 4 (aP2), and stearoylCoA desaturase. Moreover, an FP receptor agonist, Fluprostenol, suppressed the expression of those adipogenic genes in 3T3-L1 cells; whereas an FP receptor antagonist, AL-8810, efficiently inhibited the suppression of adipogenesis caused by the endogenous PGF 2␣ . These results indicate that AKR1B3 acts as the PGFS in adipocytes and that AKR1B3-produced PGF 2␣ suppressed adipocyte differentiation by acting through FP receptors.

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Section: Akr1b3 As Pgfs In Adipocytessupporting

confidence: 92%

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Fujimori

Ueno

Nagata

et al. 2010

Journal of Biological Chemistry

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“…When applied to an inhibitor study, the correlation analysis profiled the relationship of lipid mediators with regard to dependency on enzymes of the pathway. It has been discussed that various terminal PG synthases are differentially coupled with COX-1 and COX-2 [23][24][25]. However, we did not observe selective inhibition of specific PG species by COX inhibitors (Figs.…”

Section: Discussioncontrasting

confidence: 50%

Pathway-oriented profiling of lipid mediators in macrophages

Kita

Takahashi

Uozumi

et al. 2005

Biochemical and Biophysical Research Communications

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Macrophages produce various kinds of lipid mediators including eicosanoids and platelet-activating factor. Since they are produced from common precursors, arachidonic acid-containing phospholipids, regulations of metabolic pathways underlie the patterning of lipid mediator production. Here, we report a pathway-oriented profiling strategy of lipid mediators by a newly developed multiplex quantification system. We profiled mouse peritoneal macrophages in different activation states. The analysis of kinetics revealed the differences in the production time course of various lipid mediators, which also differed by the macrophage types. Scatterplot matrix analysis of the inhibitor study revealed correlations of lipid mediator species. The changes of these correlations provided estimates on the effects of lipopolysaccharide priming. We also found a highly linked production of 11-hydroxyeicosatetraenoic acid and prostaglandin E 2 , implying the in vivo property of cyclooxygenasemediated 11-hydroxyeicosatetraenoic acid production. The present approach will serve as a strategy for understanding the regulatory mechanism of lipid mediator production.

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“…Using an experimental model of germinal center (GC) reactions that included HK cells, we identified the PG species that are produced by FDCs. We found that human FDCs express PGI 2 and PGE 2 synthases and that HK cells produce PGI 2 and PGE 2 (8,13). In our model, PGI 2 and PGE 2 , as well as HK cells, inhibit proliferation and apoptosis of T cells (8) and enhance survival of GC B cells (14).…”

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confidence: 76%

“…Arachidonic acid released from membrane phospholipids is converted to PG via sequential enzymatic processes. Cyclooxygenase (COX)-1 or COX-2 mediates the conversion of arachidonic acid to PGH 2 , which is transformed into PGE 2 , PGI 2 , PGD 2 , or PGF 2a by respective tissue-and cell-specific PG synthases (2). The expression of COX-1 is constitutive, whereas COX-2 expression is induced by various triggers, including inflammatory stimuli.…”

mentioning

confidence: 99%

Suppressor of Cytokine Signaling 1 Is a Positive Regulator of TGF-β–Induced Prostaglandin Production in Human Follicular Dendritic Cell–like Cells

Cho

Kim

et al. 2015

The Journal of Immunology

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PGs are emerging as important immune modulators. Since our report on the expression of PG synthases in human follicular dendritic cells, we investigated the potential immunoregulatory function of PGs and their production mechanisms. In this study, we explored the intracellular signaling molecules mediating TGF-β–induced cyclooxygenase (COX)-2 augmentation in follicular dendritic cell–like cells. TGF-β triggered phosphorylation of Smad3 and ERK, which were essential for the increase in COX-2 protein. Interestingly, depletion of suppressor of cytokine signaling 1 (SOCS1) resulted in an almost complete inhibition of Smad3 phosphorylation and COX-2 induction. Nuclear translocation of Smad3 was inhibited in SOCS1-depleted cells. SOCS1 knockdown also downregulated TGF-β–stimulated Snail expression and its binding to the Cox-2 promoter. In contrast, overexpression of SOCS1 gave rise to a significant increase in Snail and COX-2 proteins. SOCS1 was reported to be a negative regulator of cytokine signaling by various investigators. However, our current data suggest that SOCS1 promotes TGF-β–induced COX-2 expression and PG production by facilitating Smad3 phosphorylation and Snail binding to the Cox-2 promoter. The complete understanding of the biological function of SOCS1 might be obtained via extensive studies with diverse cell types.

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Coupling between cyclooxygenases and prostaglandin F2α synthase

Cited by 16 publications

References 29 publications

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Suppression of Adipocyte Differentiation by Aldo-keto Reductase 1B3 Acting as Prostaglandin F2α Synthase

Pathway-oriented profiling of lipid mediators in macrophages

Suppressor of Cytokine Signaling 1 Is a Positive Regulator of TGF-β–Induced Prostaglandin Production in Human Follicular Dendritic Cell–like Cells

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