Regulation of Arachidonic Acid Release by Calcium Influx in Human Endothelial Cells

Brussel, Elisabeth Millanvoye-Van; David‐Dufilho, Monique; Pham, Thuc Do; Iouzalen, Lahcen; Devynck, Marie‐Aude

doi:10.1159/000025647

Cited by 29 publications

(17 citation statements)

References 33 publications

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“…Activation of cPLA 2 ␣ involves phosphorylation of the enzyme, which enhances its activity and its translocation to the ER, Golgi, and nuclear membranes, where it hydrolyzes arachidonate-containing phospholipids to release AA (28,29). We first examined the effect of CD36 on cPLA 2 ␣ translocation by comparing the cPLA 2 ␣ content of membrane fractions prepared by differen-FIGURE 2.…”

Section: Resultsmentioning

confidence: 99%

“…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). The cPLA 2 ␣ enzyme is regulated through a series of phosphorylation events leading to its activation and translocation to the endoplasmic reticulum, where it selectively hydrolyzes phospholipids containing AA at the sn-2 position (29).…”

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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: Resultsmentioning

confidence: 99%

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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“…The increase of cytosolic Ca 2ϩ concentration in ECs initiates the production of endothelium-derived relaxing factors, including nitric oxide (NO) (2,8,35). In TR␣ KO mice, concurrent inhibition of NO and prostacyclin strongly enhanced high-K ϩ -induced CA contraction, suggesting that ECs are releasing more NO and prostacyclin to mask augmented contraction in CAs from TR␣ KO mice (Fig.…”

Section: Discussionmentioning

confidence: 99%

Thyroid hormone receptor-α and vascular function

Wang¹,

Scott²,

Yuan

et al. 2012

American Journal of Physiology-Cell Physiology

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Thyroid hormone (TH) treatment exerts beneficial effects on the cardiovascular system: it lowers cholesterol and LDL levels and enhances cardiac contractile function. However, little is known about the effect of TH on vascular function or the functional role of TH receptors (TRs) in the regulation of vascular tone. We have investigated the contribution of TRs to vascular contractility in the heart. Among different TR subtype-specific knockout (KO) mice, vascular contraction was significantly enhanced in coronary arteries isolated from TRα KO compared with wild-type mice, while chronic TH treatment significantly attenuated coronary vascular contraction. We found that TRα is the predominant TR in mouse coronary smooth muscle cells (SMCs). Coronary SMCs isolated from TRα KO mice exhibited a significant decrease in K+channel activity, whereas TH treatment increased K+channel activity in a dose-dependent manner. These data suggest that TRα in SMCs has prominent effects on regulation of vascular tone and TH treatment helps decrease coronary vascular tone by increasing K+channel activity through TRα in SMCs.

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“…Data represent mean Ϯ S.E.M. ; n ϭ 5. ticulum by a calcium-dependent mechanism (Nalefski et al, 1994;Freeman et al, 1998;Millanvoye-Van Brussel et al, 1999;Duan et al, 2008). To gain insight into the involvement of H 2 S in cPLA 2 activation, we performed an immunofluorescence study using the mesenteric artery.…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide-Induced Dual Vascular Effect Involves Arachidonic Acid Cascade in Rat Mesenteric Arterial Bed

Bianca

Sorrentino²,

Coletta³

et al. 2011

J Pharmacol Exp Ther

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Hydrogen sulfide (H 2 S), a novel gaseous transmitter, is considered a physiological regulator of vascular homeostasis. Recent evidence suggests H 2 S as an endothelium-hyperpolarizing factor (EDHF) candidate. To address this issue, we evaluated the vascular effect of sodium hydrogen sulfide (NaHS), an H 2 S donor, on the rat mesenteric arterial bed. NaHS concentrationresponse curve was performed on preconstricted mesenteric arterial bed. To assess the contribution of EDHF, we performed a pharmacologic dissection using indomethacin, N G -nitro-Larginine methyl ester (L-NAME), or apamin and charybdotoxin as cyclooxygenase, nitric-oxide synthase, and calcium-dependent potassium channel inhibitors, respectively. In another set of experiments, we used 4-(4-octadecylphenyl)-4-oxobutenoic acid, baicalein, or proadifen as phospholipase A 2 (PLA 2 ), lipoxygenase, and cytochrome P450 inhibitors, respectively. Finally, an immunofluorescence study was performed to support the involvement of PLA 2 in mesenteric artery challenged by NaHS. NaHS promoted a dual vascular effect (i.e., vasoconstriction and vasodilation). L-NAME or baicalein administration affected neither NaHS-mediated vasodilation nor vasoconstriction, whereas apamin and charybdotoxin significantly inhibited NaHS-induced relaxation. Pretreatment with PLA 2 inhibitor abolished both the contracting and the relaxant effect, whereas P450 cytochrome blocker significantly reduced NaHS-mediated relaxation. The immunofluorescence study showed that NaHS caused a migration of cytosolic PLA 2 close to the nucleus, which implicates activation of this enzyme. Our data indicate that H 2 S could activate PLA 2 , which in turn releases arachidonic acid leading, initially, to vasoconstriction followed by vasodilation mediated by cytochrome P450-derived metabolites. Because EDHF has been presumed to be a cytochrome P450 derivative of the arachidonic acid, our results suggest that H 2 S acts through EHDF release.

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Regulation of Arachidonic Acid Release by Calcium Influx in Human Endothelial Cells

Cited by 29 publications

References 33 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

Thyroid hormone receptor-α and vascular function

Hydrogen Sulfide-Induced Dual Vascular Effect Involves Arachidonic Acid Cascade in Rat Mesenteric Arterial Bed

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