# Convergence of the Cox-2 and 5-Lipoxygenase Pathways

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $312,510

## Abstract

Abstract
The reaction of arachidonic acid with cyclooxygenase or lipoxygenase gives rise to prostaglandins and
leukotrienes, respectively. These eicosanoids are important regulators of homeostatic and pathophysiologic
processes, including inflammation and cancer. We have previously described a unique catalytic activity of the
inducible isoform of cyclooxygenase, COX-2, in a reaction with the 5-lipoxygenase product, 5-hydroxy-
arachidonic acid. COX-2 catalyzed oxygenation of 5-hydroxy-arachidonic acid gives rise to hemiketal (HK)
eicosanoids as well as 5-hydroxy-prostaglandins (5-OH-PGs). Both groups of eicosanoids were discovered by
us, the latter only very recently. We hypothesize that these novel eicosanoids act as autocrine and paracrine
regulators of myeloid, lymphoid, and endothelial cell function. We will analyze the role of HKs and 5-OH-PGs in
endothelial cell tubulogenesis, T cell activation and differentiation, receptor binding and activation, kinase
signaling, and platelet aggregation. In specific aim 1 we will test the hypothesis that HKs mediate endothelial
cell tubulogenesis and migration through kinase signaling. We will also analyze how HKs mediate T cell
activation and differentiation. In specific aim 2 we will test the hypothesis that 5-OH-PGs bind traditional PG
receptors and mediate signaling. Preliminary studies have shown that 5-OH-PGs bind at EP receptors and
have an effect on platelet aggregation. To test this hypothesis we will determine the binding affinity of 5-OH-
PGs at human prostanoid receptors and determine their signal transduction as agonists or antagonists. In
specific aim 3 we will analyze the effect of 5-OH-PGs on the aggregation of human platelets. Our studies will
substantially expand the range of eicosanoids formed specifically by COX-2. Elucidation of the biological
activities of the novel eicosanoids will help better understand the function of their biosynthetic enzymes in
inflammation as well as the therapeutic effects of the drugs used to inhibit prostaglandin and leukotriene
biosynthesis.

## Key facts

- **NIH application ID:** 10142484
- **Project number:** 5R01GM076592-13
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Claus Schneider
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $312,510
- **Award type:** 5
- **Project period:** 2007-01-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10142484

## Citation

> US National Institutes of Health, RePORTER application 10142484, Convergence of the Cox-2 and 5-Lipoxygenase Pathways (5R01GM076592-13). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10142484. Licensed CC0.

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