Regulation and Functions of 15-Lipoxygenases in Human Macrophages

Snodgrass, Ryan G.; Brüne, Bernhard

doi:10.3389/fphar.2019.00719

Cited by 108 publications

(85 citation statements)

References 101 publications

(160 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another pathway of inflammatory response in the human body is the lipoxygenase (LOX) pathway. Here, long-chain polyunsaturated fatty acids, such as arachidonic acid, are enzymatically peroxidized by lipoxygenases to the corresponding hydroperoxyl derivatives to produce eicosanoid signaling metabolites ( Figure 3 ) [ 47 ].…”

Section: Introductionmentioning

confidence: 99%

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Schultz

Osuji

Wack

et al. 2021

Plants

View full text Add to dashboard Cite

Our study investigates 16 medicinal plants via assessment of inhibition of proinflammatory enzymes such as cyclooxygenases (COX). The plants are used by traditional healers in the Greater Mpigi region in Uganda to treat inflammation and related disorders. We present results of diverse in vitro experiments performed with 76 different plant extracts, namely, (1) selective COX-2 and COX-1 inhibitor screening; (2) 15-LOX inhibition screening; (3) antibacterial resazurin assay against multidrug-resistant Staphylococcus aureus, Listeria innocua, Listeria monocytogenes, and Escherichia coli K12; (4) DPPH assay for antioxidant activity; and (5) determination of the total phenolic content (TPC). Results showed a high correlation between traditional use and pharmacological activity, e.g., extracts of 15 out of the 16 plant species displayed significant selective COX-2 inhibition activity in the PGH2 pathway. The most active COX-2 inhibitors (IC50 < 20 µg/mL) were nine extracts from Leucas calostachys, Solanum aculeastrum, Sesamum calycinum subsp. angustifolium, Plectranthus hadiensis, Morella kandtiana, Zanthoxylum chalybeum, and Warburgia ugandensis. There was no counteractivity between COX-2 and 15-LOX inhibition in these nine extracts. The ethyl acetate extract of Leucas calostachys showed the lowest IC50 value with 0.66 µg/mL (COX-2), as well as the most promising selectivity ratio with 0.1 (COX-2/COX-1). The TPCs and the EC50 values for DPPH radical scavenging activity showed no correlation with COX-2 inhibitory activity. This led to the assumption that the mechanisms of action are most likely not based on scavenging of reactive oxygen species and antioxidant activities. The diethyl ether extract of Harungana madagascariensis stem bark displayed the highest growth inhibition activity against S. aureus (MIC value: 13 µg/mL), L. innocua (MIC value: 40 µg/mL), and L. monocytogenes (MIC value: 150 µg/mL). This study provides further evidence for the therapeutic use of the previously identified plants used medicinally in the Greater Mpigi region.

show abstract

Section: Introductionmentioning

confidence: 99%

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Schultz

Osuji

Wack

et al. 2021

Plants

View full text Add to dashboard Cite

show abstract

“…The involvement of the NOTCH signaling pathway in the overexpression of the NOTCH1 receptor and its ligand DLL1 plays a fundamental role in the development of endometrial arteries and maximizes reproductive success in mice [52]. The LPS injection also upregulated the ALOX15 gene (logFC = 1.71) whose product controls cytokine generation [53], induces the proliferation of tumor cells and the dysregulation of angiogenesis. The adverse effects of ALOX15 can be mitigated by the overexpression of cPLA2.…”

Section: Discussionmentioning

confidence: 99%

Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

Paukszto

Mikołajczyk

Jastrzebski

et al. 2020

IJMS

View full text Add to dashboard Cite

Endometrial infections at a young age can lead to fertility issues in adulthood. Bacterial endotoxins, such as lipopolysaccharide (LPS), can participate in long-term molecular changes even at low concentrations. Lipopolysaccharide plays a crucial role in the progression of septic shock, inflammation and auto-immune diseases. The aim of this study was to describe transcriptomic modulations in the porcine endometrium, induced in vivo by a single subclinical dose of LPS from Salmonella Enteritidis. which did not produce clinical symptoms of toxicity. The RNA-seq methodology was applied to reveal 456 differentially expressed regions, including 375 genes, four long noncoding RNAs, and 77 other unclassified transcripts. Two independent methods confirmed 118 alternatively spliced genes that participate i.a., in the formation of the MHC-I complex and the adaptive immune response. Single nucleotide variant-calling algorithms supported the identification of 3730 allele-specific expression variants and 57 canonical A-to-I RNA editing sites. The results demonstrated that the differential expression of genes involved in inflammation, immune response, angiogenesis and endometrial development may be maintained for up to 7 days after exposure to LPS. RNA editing sites and long noncoding RNAs (lncRNAs) play an important role in transcriptional regulatory machinery in the porcine endometrium in response to LPS administration.

show abstract

“…This complex facilitates 15-LOX activity on PL-esterified PUFA and is proposed to play regulatory roles in ferroptosis along with GPX. PEPB1 has been suggested to direct 15-LOX activity toward PL substrates when free AA is depleted (55). The crystal structure of human 15-LOX-2 (ALOX15B) revealed a hydrophobic loop in the N-terminal domain that is flanked by calcium binding sites, a feature that is absent in 5-LOX (42).…”

Section: Structure and Membrane Association Of Mammalian Loxsmentioning

confidence: 99%

“…The preference of human 15-LOX orthologs is: DHA > EPA > AA > GLA > LA (18). One key difference is that 15-LOX-1 (ALOX15) possesses dual positional specificity for some of its substrates (e.g., 12 and 15-lipoxygenase activities for AA), whereas 15-LOX-2 (ALOX15B) exhibits singular specificity (15-lipoxygenase activity) (55). The hydroperoxide isomerase and epoxidase activities of 15-LOX-1 (ALOX15) are proposed to function in the synthesis of eoxins, E-series resolvins, and protectin from their respective precursors.…”

Section: Loxs Act On a Broad Range Of Substratesmentioning

confidence: 99%

The Biosynthesis of Enzymatically Oxidized Lipids

et al. 2020

View full text Add to dashboard Cite

Enzymatically oxidized lipids are a specific group of biomolecules that function as key signaling mediators and hormones, regulating various cellular and physiological processes from metabolism and cell death to inflammation and the immune response. They are broadly categorized as either polyunsaturated fatty acid (PUFA) containing (free acid oxygenated PUFA “oxylipins”, endocannabinoids, oxidized phospholipids) or cholesterol derivatives (oxysterols, steroid hormones, and bile acids). Their biosynthesis is accomplished by families of enzymes that include lipoxygenases (LOX), cyclooxygenases (COX), cytochrome P450s (CYP), and aldo-keto reductases (AKR). In contrast, non-enzymatically oxidized lipids are produced by uncontrolled oxidation and are broadly considered to be harmful. Here, we provide an overview of the biochemistry and enzymology of LOXs, COXs, CYPs, and AKRs in humans. Next, we present biosynthetic pathways for oxylipins, oxidized phospholipids, oxysterols, bile acids and steroid hormones. Last, we address gaps in knowledge and suggest directions for future work.

show abstract

Regulation and Functions of 15-Lipoxygenases in Human Macrophages

Cited by 108 publications

References 101 publications

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Antiinflammatory Medicinal Plants from the Ugandan Greater Mpigi Region Act as Potent Inhibitors in the COX-2/PGH2 Pathway

Transcriptome, Spliceosome and Editome Expression Patterns of the Porcine Endometrium in Response to a Single Subclinical Dose of Salmonella Enteritidis Lipopolysaccharide

The Biosynthesis of Enzymatically Oxidized Lipids

Contact Info

Product

Resources

About