Directing eicosanoid esterification into phospholipids

O'Donnell, Valerie Bridget; Murphy, Robert C.

doi:10.1194/jlr.c075986

Cited by 7 publications

(5 citation statements)

References 25 publications

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“…While 9-HSA was detected in all phospholipid classes examined, in relative terms, presence of the fatty acid in PE predominated. This is consistent with previous data in platelets showing that PE phospholipids are prone to contain oxidized fatty acids derived from arachidonic acid [14,15,16]. Consistent with the sharp decreases of 9-HSA already observed with GC/MS (Figure 3), tumor samples showed a general decrease in all phospholipid classes examined.…”

Section: Resultssupporting

confidence: 92%

Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death

Rodríguez

Guijas

Astudillo

et al. 2019

Cancers

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Hydroxy fatty acids are known to cause cell cycle arrest and apoptosis. The best studied of them, 9-hydroxystearic acid (9-HSA), induces apoptosis in cell lines by acting through mechanisms involving different targets. Using mass spectrometry-based lipidomic approaches, we show in this study that 9-HSA levels in human colorectal tumors are diminished when compared with normal adjacent tissue. Since this decrease could be compatible with an escape mechanism of tumors from 9-HSA-induced apoptosis, we investigated different features of the utilization of this hydroxyfatty acid in colon. We show that in colorectal tumors and related cell lines such as HT-29 and HCT-116, 9-HSA is the only hydroxyfatty acid constituent of branched fatty acid esters of hydroxyfatty acids (FAHFA), a novel family of lipids with anti-inflammatory properties. Importantly, FAHFA levels in tumors are elevated compared with normal tissue and, unlike 9-HSA, they do not induce apoptosis of colorectal cell lines over a wide range of concentrations. Further, the addition of 9-HSA to colon cancer cell lines augments the synthesis of different FAHFA before the cells commit to apoptosis, suggesting that FAHFA formation may function as a buffer system that sequesters the hydroxyacid into an inactive form, thereby restricting apoptosis.

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Section: Resultssupporting

confidence: 92%

Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death

Rodríguez

Guijas

Astudillo

et al. 2019

Cancers

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“…In response to external stimuli (e.g. bradykinin, thrombin, inflammatory insult), PUFAs (5) and oxylipins (6) are released from membrane phospholipids by phospholipases including phospholipase A2 (PLA2). Of note, hundreds of structurally and strereochemically distinct oxylipins can be produced from AA and other PUFAs.…”

Section: Introductionmentioning

confidence: 99%

MS-based targeted metabolomics of eicosanoids and other oxylipins: Analytical and inter-individual variabilities

Gladine

Ostermann

Newman

et al. 2019

Free Radical Biology and Medicine

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HAL is a multi-disciplinary open access archive for the deposit and dissemination of scientific research documents, whether they are published or not. The documents may come from teaching and research institutions in France or abroad, or from public or private research centers. L'archive ouverte pluridisciplinaire HAL, est destinée au dépôt et à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

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“…It is known that various PLA2s are responsible for the release of AA and DHA in astrocytes [ 58 ]. Some of the oxylipins can be included in the composition of phospholipids and released by them [ 6 ]. Therefore, it is difficult to directly relate solely the oxylipins released into the extracellular medium, with their enzymatic synthesis.…”

Section: Discussionmentioning

confidence: 99%

“…The conversion of PUFAs into oxylipins occurs via four major pathways, involving cyclooxygenases (COX), lipoxygenases (LOX), and cytochrome P450 monooxygenases (CYP450), and non-enzymatically [ 1 , 4 , 5 ]. When cells are stimulated, it is important that different PUFAs, and even some of their derivatives, are released from membrane phospholipids and metabolized into oxylipins simultaneously [ 6 , 7 ]. Therefore, there is a competition between pathways for their substrates [ 1 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

High Glucose Shifts the Oxylipin Profiles in the Astrocytes towards Pro-Inflammatory States

et al. 2021

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Hyperglycemia is associated with several complications in the brain, which are also characterized by inflammatory conditions. Astrocytes are responsible for glucose metabolism in the brain and are also important participants of inflammatory responses. Oxylipins are lipid mediators, derived from the metabolism of polyunsaturated fatty acids (PUFAs) and are generally considered to be a link between metabolic and inflammatory processes. High glucose exposure causes astrocyte dysregulation, but its effects on the metabolism of oxylipins are relatively unknown and therefore, constituted the focus of our work. We used normal glucose (NG, 5.5 mM) vs. high glucose (HG, 25 mM) feeding media in primary rat astrocytes-enriched cultures and measured the extracellular release of oxylipins (UPLC-MS/MS) in response to lipopolysaccharide (LPS). The sensitivity of HG and NG growing astrocytes in oxylipin synthesis for various serum concentrations was also tested. Our data reveal shifts towards pro-inflammatory states in HG non-stimulated cells: an increase in the amounts of free PUFAs, including arachidonic (AA), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, and cyclooxygenase (COX) mediated metabolites. Astrocytes cultivated in HG showed a tolerance to the LPS, and an imbalance between inflammatory cytokine (IL-6) and oxylipins release. These results suggest a regulation of COX-mediated oxylipin synthesis in astrocytes as a potential new target in treating brain impairment associated with hyperglycemia.

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Directing eicosanoid esterification into phospholipids

Cited by 7 publications

References 25 publications

Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death

Sequestration of 9-Hydroxystearic Acid in FAHFA (Fatty Acid Esters of Hydroxy Fatty Acids) as a Protective Mechanism for Colon Carcinoma Cells to Avoid Apoptotic Cell Death

MS-based targeted metabolomics of eicosanoids and other oxylipins: Analytical and inter-individual variabilities

High Glucose Shifts the Oxylipin Profiles in the Astrocytes towards Pro-Inflammatory States

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