Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells

Golej, Deidre L.; Askari, Bardia; Kramer, Farah; Barnhart, Shelley; Vivekanandan-Giri, Anuradha; Pennathur, Subramaniam; Bornfeldt, Karin E.

doi:10.1194/jlr.m013292

Cited by 130 publications

(105 citation statements)

References 47 publications

(49 reference statements)

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“…Consistent with these findings, it was recently shown in vascular cells that although acute down-regulation of ACSL4 (acyl-CoA synthetase 4), which selectively acylates AA to AA-CoA for esterification, resulted in increased PGE 2 release, the opposite response occurred (i.e. a reduction in PGE 2 release) with stable, long term reduction of ACSL4 (26).…”

Section: Discussionsupporting

confidence: 66%

“…: 314-747-0348; Fax: 314-362-8109; E-mail: NAbumrad@DOM.wustl.edu. 2 The abbreviations used are: ER, endoplasmic reticulum; AA, arachidonic acid; BEL, bromoenol lactone ((E The level of non-esterified AA is controlled by the relative activities of phospholipases, lysophospholipid acyl transferases (25), and arachidonic acid-specific CoA synthetases, such as ACSL4 (26). Cytosolic calcium-dependent phospholipase A 2 ␣ (cPLA 2 ␣) plays a major role in AA release (18,27) and is activated by increases in cytosolic calcium initially released from the ER and then sustained by calcium influx via membrane ion channels responsive to ER calcium depletion (28).…”

mentioning

confidence: 99%

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CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2

Kuda¹,

Jenkins

Skinner³

et al. 2011

Journal of Biological Chemistry

107

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The scavenger receptor FAT/CD36 contributes to the inflammation associated with diabetes, atherosclerosis, thrombosis, and Alzheimer disease. Underlying mechanisms include CD36 promotion of oxidative stress and its signaling to stress kinases. Here we document an additional mechanism for the role of CD36 in inflammation. CD36 regulates membrane calcium influx in response to endoplasmic reticulum (ER) stress, release of arachidonic acid (AA) from cellular membranes by cytoplasmic phospholipase A 2 ␣ (cPLA 2 ␣) and contributes to the generation of proinflammatory eicosanoids. CHO cells stably expressing human CD36 released severalfold more AA and prostaglandin E 2 (PGE 2 ), a major product of AA metabolism by cyclooxygenases, in response to thapsigargin-induced ER stress as compared with control cells. Calcium influx after ER calcium release resulted in phosphorylation of cPLA 2 and its translocation to membranes in a CD36-dependent manner. Peritoneal macrophages from CD36 ؊/؊ mice exhibited diminished calcium transients and reduced AA release after thapsigargin or UTP treatment with decreased ERK1/2 and cPLA 2 phosphorylation. However, PGE 2 production was unexpectedly enhanced in CD36 ؊/؊ macrophages, which probably resulted from a large induction of cyclooxygenase 2 mRNA and protein. The data demonstrate participation of CD36 in membrane calcium influx in response to ER stress or purinergic receptor stimulation resulting in AA liberation for PGE 2 formation. Collectively, these results identify a mechanism contributing to the pleiotropic proinflammatory effects of CD36 and suggest that its targeted inhibition may reduce the acute inflammatory response.

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Section: Discussionsupporting

confidence: 66%

mentioning

confidence: 99%

CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2

Kuda¹,

Jenkins

Skinner³

et al. 2011

Journal of Biological Chemistry

107

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“…Mammalian ACSL4 has a substrate preference for arachidonic acid (C20:4) and eicosapentaenoic acid (C20:5) (Golej et al, 2011;Kang et al, 1997). C20 and C22 polyunsaturated fatty acids are absent in Drosophila (Shen et al, 2010).…”

Section: Acsl Regulates Brain Fatty Acid Compositionmentioning

confidence: 99%

“…Many studies have reported that both rat ACSL4 and Drosophila Acsl are enriched in the ER (Lewin et al, 2002;Meloni et al, 2009;O'Sullivan et al, 2012;Zhang et al, 2009), suggesting that they have a role in lipid synthesis. Indeed, both ACSL4 and Acsl positively regulate lipid biosynthesis (Golej et al, 2011;Kuch et al, 2014;Zhang et al, 2009). In addition, ACSL4 is also enriched in peroxisomes of rat liver (Lewin et al, 2002).…”

Section: Acsl Enzymatic Activity Is Required For Nmj Developmentmentioning

confidence: 99%

“…ACSs convert free fatty acids into acyl-CoAs for lipid synthesis, fatty acid degradation or membrane lipid remodeling (Mashek et al, 2007). For example, ACSL4 converts long-chain fatty acids (LCFAs; aliphatic tails longer than 12 carbons), preferentially arachidonic acid (C20:4), into LCFA-CoAs that are incorporated into glycerol-phospholipids (GPLs) and neutral lipids in non-neuronal cells (Golej et al, 2011;Kuch et al, 2014). The mechanism of how fatty acids and fatty-acid-modifying enzymes affect lipid composition, and thereby modulate development processes, is beginning to be understood in lower model organisms (Kniazeva et al, 2012;Zhang et al, 2011;Zhu et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

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Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids

Huang

Lam

et al. 2016

Journal of Cell Science

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Nervous system development and function are tightly regulated by metabolic processes, including the metabolism of lipids such as fatty acids. Mutations in long-chain acyl-CoA synthetase 4 (ACSL4) are associated with non-syndromic intellectual disabilities. We previously reported that Acsl, the Drosophila ortholog of mammalian ACSL3 and ACSL4, inhibits neuromuscular synapse growth by suppressing bone morphogenetic protein (BMP) signaling. Here, we report that Acsl regulates the composition of fatty acids and membrane lipids, which in turn affects neuromuscular junction (NMJ) synapse development. Acsl mutant brains had a decreased abundance of C16:1 fatty acyls; restoration of Acsl expression abrogated NMJ overgrowth and the increase in BMP signaling. A lipidomic analysis revealed that Acsl suppressed the levels of three lipid raft components in the brain, including mannosyl glucosylceramide (MacCer), phosphoethanolamine ceramide and ergosterol. The MacCer level was elevated in Acsl mutant NMJs and, along with sterol, promoted NMJ overgrowth, but was not associated with the increase in BMP signaling in the mutants. These findings suggest that Acsl inhibits NMJ growth by stimulating C16:1 fatty acyl production and concomitantly suppressing raft-associated lipid levels.

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Lipid droplets provide metabolic flexibility for cancer progression

Safi,

Menéndez,

Pol

2024

FEBS Letters

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A hallmark of cancer cells is their remarkable ability to efficiently adapt to favorable and hostile environments. Due to a unique metabolic flexibility, tumor cells can grow even in the absence of extracellular nutrients or in stressful scenarios. To achieve this, cancer cells need large amounts of lipids to build membranes, synthesize lipid‐derived molecules, and generate metabolic energy in the absence of other nutrients. Tumor cells potentiate strategies to obtain lipids from other cells, metabolic pathways to synthesize new lipids, and mechanisms for efficient storage, mobilization, and utilization of these lipids. Lipid droplets (LDs) are the organelles that collect and supply lipids in eukaryotes and it is increasingly recognized that the accumulation of LDs is a new hallmark of cancer cells. Furthermore, an active role of LD proteins in processes underlying tumorigenesis has been proposed. Here, by focusing on three major classes of LD‐resident proteins (perilipins, lipases, and acyl‐CoA synthetases), we provide an overview of the contribution of LDs to cancer progression and discuss the role of LD proteins during the proliferation, invasion, metastasis, apoptosis, and stemness of cancer cells.

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Long-chain acyl-CoA synthetase 4 modulates prostaglandin E2 release from human arterial smooth muscle cells

Cited by 130 publications

References 47 publications

CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2

CD36 Protein Is Involved in Store-operated Calcium Flux, Phospholipase A2 Activation, and Production of Prostaglandin E2

Acsl, the Drosophila ortholog of intellectual-disability-related ACSL4, inhibits synaptic growth by altered lipids

Lipid droplets provide metabolic flexibility for cancer progression

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