Different modulation of phospholipase A2 activity by saturated and monounsaturated N-acylethanolamines

Zolese, Giovanna; Woźniak, Michał; Mariani, Paolo; Saturni, Letizia; Bertoli, Enrico; Ambrosini, Annarina

doi:10.1194/jlr.m200395-jlr200

Cited by 18 publications

(25 citation statements)

References 63 publications

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“…Moreover, increased levels of secretory PLA 2 have been reported in inflammatory tissues (25) and in several tumor types (26). We demonstrated that the acyl chain length and/or the presence of a single double bond was crucial both for the NAE interaction with the lipid bilayer and for the effect exerted on enzymatic activity (18).…”

mentioning

confidence: 95%

“…On the other hand, NAEs, with saturated and monounsaturated acyl chains, present some biological activities but are thought to be inactive towards cannabinoid (CB) receptors (13,14). The chemical nature of these NAEs and experimental evidence (15)(16)(17)(18)(19) suggest that some of their biological effects could be related, at least in part, to physical interactions with the lipidic part of the membrane. Because AEA is a largely hydrophobic molecule, it is possible that its local concentration in close proximity to the cannabinoid receptor binding site, which is localized within the lipid bilayer (20), may be considerably higher than that in aqueous environments outside the cells (21).…”

mentioning

confidence: 99%

“…Moreover, we demonstrated that saturated and monounsaturated NAEs affect the activity of a secretory phospholipase A 2 (18) that is largely dependent on the structural, physicochemical, and dynamic properties of the lipid bilayer (22)(23)(24). Secretory PLA 2 s are a family of water-soluble enzymes (13)(14)(15) that are structurally and mechanistically related.…”

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confidence: 99%

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On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

Ambrosi

Ragni

Ambrosini

et al. 2005

Journal of Lipid Research

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The acylethanolamide anandamide (AEA) occurs in a variety of mammalian tissues and, as a result of its action on cannabinoid receptors, exhibits several cannabimimetic activities. Moreover, some of its effects are mediated through interaction with an ion channel-type vanilloid receptor. However, the chemical features of AEA suggest that some of its biological effects could be related to physical interactions with the lipidic part of the membrane. The present work studies the effect of AEA-induced structural modifications of the dipalmitoylphosphatidylcholine (DPPC) bilayer on phospholipase A 2 (PLA 2 ) activity, which is strictly dependent on lipid bilayer features. This study, performed by 2-dimethylamino-(6-lauroyl)-naphthalene fluorescence, demonstrates that the effect of AEA on PLA 2 activity is concentration-dependent. In fact, at low AEA/DPPC molar ratios (from R ‫؍‬ 0.001 to R ‫؍‬ 0.04), there is an increase of the enzymatic activity, which is completely inhibited for R ‫؍‬ 0.1. X-ray diffraction data indicate that the AEA affects DPPC membrane structural properties in a concentration-dependent manner. Because the biphasic effect of increasing AEA concentrations on PLA 2 activity is related to the induced modifications of membrane bilayer structural properties, we suggest that AEA-phospholipid interactions may be important to produce, at least in part, some of the similarly biphasic responses of some physiological activities to increasing concentrations of AEA. -Ambrosi, S

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confidence: 95%

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confidence: 99%

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confidence: 99%

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On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

Ambrosi

Ragni

Ambrosini

et al. 2005

Journal of Lipid Research

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“…In line with these data, it has been already demonstrated that GP values are independent of the phospholipid headgroup 40 and that the physical interaction of different N-acylethanolamines (NAEs) with lipid membranes can modify the lipid T m with a pattern dependent on the length of their acyl chain and on the number of double bonds. 17,41 Moreover, it has been shown that unsaturated NAEs slightly broaden the T m range, an effect that might be related to the formation of lateral domains of the membrane with different lipid composition. 41 Previous data have indicated that the interaction of LOXs with model membranes can induce an overall stabilization of both the protein and the membrane.…”

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confidence: 99%

“…17,41 Moreover, it has been shown that unsaturated NAEs slightly broaden the T m range, an effect that might be related to the formation of lateral domains of the membrane with different lipid composition. 41 Previous data have indicated that the interaction of LOXs with model membranes can induce an overall stabilization of both the protein and the membrane. 28,29 Here, to dissect the effects of LOX-1 protein matrix from its enzyme activity on membrane properties, we used DPPC liposomes devoid of LOX-1 substrates, as well as AEA-containing LUVs incubated with the inactive apo-form of the enzyme.…”

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confidence: 99%

Impact of Embedded Endocannabinoids and Their Oxygenation by Lipoxygenase on Membrane Properties

Dainese

Sabatucci

Angelucci

et al. 2012

ACS Chem. Neurosci.

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N-Arachidonoylethanolamine (anandamide) and 2-arachidonoylglycerol are the best characterized endocannabinoids. Their biological activity is subjected to metabolic control whereby a dynamic equilibrium among biosynthetic, catabolic, and oxidative pathways drives their intracellular concentrations. In particular, lipoxygenases can generate hydroperoxy derivatives of endocannabinoids, endowed with distinct activities within cells. The in vivo interaction between lipoxygenases and endocannabinoids is likely to occur within cell membranes; thus, we sought to ascertain whether a prototypical enzyme like soybean (Glycine max) 15-lipoxygenase-1 is able to oxygenate endocannabinoids embedded in synthetic vesicles and how these substances could affect the binding ability of the enzyme to different lipid bilayers. We show that (i) embedded endocannabinoids increase membrane fluidity; (ii) 15-lipoxygenase-1 preferentially binds to endocannabinoid-containing bilayers; and that (iii) 15-lipoxygenase-1 oxidizes embedded endocannabinoids and thus reduces fluidity and local hydration of membrane lipids. Together, the present findings reveal further complexity in the regulation of endocannabinoid signaling within the central nervous system, disclosing novel control by oxidative pathways.

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Differential effects of two phospholipase D inhibitors, 1-butanol and N-acylethanolamine, on in vivo cytoskeletal organization and Arabidopsis seedling growth

et al. 2005

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Plant development is regulated by numerous chemicals derived from a multitude of metabolic pathways. However, we know very little about the biological effects and functions of many of these metabolites in the cell. N-Acylethanolamines (NAEs) are a group of lipid mediators that play important roles in mammalian physiology. Despite the intriguing similarities between animals and plants in NAE metabolism and perception, not much is known about the precise function of these metabolites in plant physiology. In plants, NAEs have been shown to inhibit phospholipase Dalpha (PLDalpha) activity, interfere with abscisic acid-induced stomatal closure, and retard Arabidopsis seedling development. 1-Butanol, an antagonist of PLD-dependent phosphatidic acid production, was reported to induce defects in Arabidopsis seedling development that were somewhat similar to effects induced by elevated levels of NAE. This raised the possibility that the impact of NAE on seedling growth could be mediated in part via its influence on PLD activity. To begin to address this possibility, we conducted a detailed, comparative analysis of the effects of 1-butanol and N-lauroylethanolamine (NAE 12:0) on Arabidopsis root cell division, in vivo cytoskeletal organization, seed germination, and seedling growth. Although both NAE 12:0 and 1-butanol induced profound cytoskeletal and morphological alterations in seedlings, there were distinct differences in their overall effects. 1-Butanol induced more pronounced modifications in cytoskeletal organization, seedling growth, and cell division at concentrations severalfold higher than NAE 12:0. We propose that these compounds mediate their differential effects on cellular organization and seedling growth, in part through the differential modulation of specific PLD isoforms.

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Different modulation of phospholipase A2 activity by saturated and monounsaturated N-acylethanolamines

Cited by 18 publications

References 63 publications

On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

On the importance of anandamide structural features for its interactions with DPPC bilayers: effects on PLA2 activity

Impact of Embedded Endocannabinoids and Their Oxygenation by Lipoxygenase on Membrane Properties

Differential effects of two phospholipase D inhibitors, 1-butanol and N-acylethanolamine, on in vivo cytoskeletal organization and Arabidopsis seedling growth

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