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

2021 ◽  
Author(s):  
Fumie Nakashima ◽  
Takashi Suzuki ◽  
Odaine N. Gordon ◽  
Dominic Golding ◽  
Toshiaki Okuno ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Degradation Product ◽  
Cyclooxygenase 2 ◽  
Eicosatetraenoic Acid ◽  
In Situ Reduction ◽  
Weak Base ◽  
Prostanoid Receptors ◽  
Cox 2 ◽  
Mediated Reduction

<p>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-PGH<sub>2</sub> that spontaneously rearranges to 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub>, the 5-hydroxy analogs of arachidonic acid derived PGE<sub>2</sub> and PGD<sub>2</sub>. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6<i>E</i>,8<i>E</i>,10<i>E</i>-enoic acid, and by SnCl<sub>2</sub>-mediated reduction to 5-OH-PGF<sub>2</sub><sub>a</sub>. Both 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub> 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 NaBH<sub>4</sub> to yield the corresponding stable 5-OH-PGF<sub>2</sub> diastereomers and enabled detection of 5-OH-PGF<sub>2</sub><sub>a</sub> in activated primary human leukocytes. 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub> were unable to activate EP and DP prostanoid receptors suggesting their bioactivity is distinct from PGE<sub>2</sub> and PGD<sub>2</sub>. </p>

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

2021 ◽  
Author(s):  
Fumie Nakashima ◽  
Takashi Suzuki ◽  
Odaine N. Gordon ◽  
Dominic Golding ◽  
Toshiaki Okuno ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Degradation Product ◽  
Cyclooxygenase 2 ◽  
Eicosatetraenoic Acid ◽  
In Situ Reduction ◽  
Weak Base ◽  
Prostanoid Receptors ◽  
Cox 2 ◽  
Mediated Reduction

<p>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-PGH<sub>2</sub> that spontaneously rearranges to 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub>, the 5-hydroxy analogs of arachidonic acid derived PGE<sub>2</sub> and PGD<sub>2</sub>. The endoperoxide was identified via its predicted degradation product, 5,12-dihydroxy-heptadecatri-6<i>E</i>,8<i>E</i>,10<i>E</i>-enoic acid, and by SnCl<sub>2</sub>-mediated reduction to 5-OH-PGF<sub>2</sub><sub>a</sub>. Both 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub> 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 NaBH<sub>4</sub> to yield the corresponding stable 5-OH-PGF<sub>2</sub> diastereomers and enabled detection of 5-OH-PGF<sub>2</sub><sub>a</sub> in activated primary human leukocytes. 5-OH-PGE<sub>2</sub> and 5-OH-PGD<sub>2</sub> were unable to activate EP and DP prostanoid receptors suggesting their bioactivity is distinct from PGE<sub>2</sub> and PGD<sub>2</sub>. </p>

Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation

2005 ◽  
Vol 288 (6) ◽  
pp. R1774-R1782 ◽  
Author(s):  
Adam Sapirstein ◽  
Hideyuki Saito ◽  
Sarah J. Texel ◽  
Tarek A. Samad ◽  
Eileen O’Leary ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase 2 ◽  
Phospholipase A ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
The Central Nervous System ◽  
Cox 2 ◽  
The Brain

The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A2α (cPLA2α) in inflammatory PGE2 production in the brain. We wondered whether cPLA2α functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA2α (cPLA2α−/−) after systemic administration of LPS. cPLA2α−/− mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA2α−/− mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA2α−/− than in cPLA2α+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA2α regulates COX-2 levels and modulates inflammatory PGE2 levels. These results indicate that cPLA2α inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.

Expression of cyclooxygenase-2 (COX-2) and p53 in neighboring invasive and in situ components of breast tumors

2012 ◽  
Vol 114 (3) ◽  
pp. 226-231 ◽  
Author(s):  
Katia Piton Serra ◽  
Luis Otavio Sarian ◽  
Raquel Mary Rodrigues-Peres ◽  
José Vassallo ◽  
Fernando Augusto Soares ◽  
...  
Keyword(s):  
Breast Tumors ◽  
Cyclooxygenase 2 ◽  
Cox 2

Cyclooxygenase-2-Mediated Metabolism of Arachidonic Acid to 15-Oxo-eicosatetraenoic Acid by Rat Intestinal Epithelial Cells

2007 ◽  
Vol 20 (11) ◽  
pp. 1665-1675 ◽  
Author(s):  
Seon Hwa Lee ◽  
Kannan Rangiah ◽  
Michelle V. Williams ◽  
Angela Y. Wehr ◽  
Raymond N. DuBois ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Cyclooxygenase 2 ◽  
Eicosatetraenoic Acid ◽  
Intestinal Epithelial

scholarly journals Unraveling how the Gly526Ser mutation arrests prostaglandin formation from arachidonic acid catalyzed by cyclooxygenase-2: a combined molecular dynamics and QM/MM study

RSC Advances ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 986-997
Author(s):  
Adrián Suñer-Rubio ◽  
Anna Cebrián-Prats ◽  
Àngels González-Lafont ◽  
José M. Lluch
Keyword(s):  
Molecular Dynamics ◽  
Arachidonic Acid ◽  
Cyclooxygenase 2 ◽  
Acid Catalyzed ◽  
Cox 2 ◽  
Derivatives Of

Gly526Ser COX-2 does not produce prostaglandins but 8,9-11,12-diepoxy derivatives of arachidonic acid.

Contribution of stromal and epithelial cells to cyclooxygenase-2 (COX-2) activity in Barrett's esophagus

2001 ◽  
Vol 120 (5) ◽  
pp. A78-A79
Author(s):  
N BUTTAR ◽  
K WANG ◽  
M ANDERSON ◽  
L LUTZKE ◽  
K KRISHNADATH
Keyword(s):  
Epithelial Cells ◽  
Barrett’S Esophagus ◽  
Barrett's Esophagus ◽  
Cyclooxygenase 2 ◽  
Cox 2

Expressions of cyclooxygenase-2 (COX-2) and prostaglandin E receptors (EPs) in gallbladder carcinoma (GBca)-association with tumor progression

2001 ◽  
Vol 120 (5) ◽  
pp. A573-A573
Author(s):  
J SHODA ◽  
T ASANO ◽  
T KAWAMOTO ◽  
Y MATSUZAKI ◽  
N TANAKA ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Gallbladder Carcinoma ◽  
Cyclooxygenase 2 ◽  
Prostaglandin E ◽  
Cox 2

Gastrin and cyclooxygenase-2 (COX-2) expression in Helicobacter pylori (Hp) infected gastric ulceration

2001 ◽  
Vol 120 (5) ◽  
pp. A727-A727
Author(s):  
S KONTUREK ◽  
P KONTUREK ◽  
W BIELANSKI ◽  
A DUDA ◽  
M ZUCHOWICZ ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Gastric Ulceration ◽  
Cyclooxygenase 2 ◽  
Cox 2
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