Hydrolysis of minor glycerophospholipids of plasma lipoproteins by human group IIA, V and X secretory phospholipases A2

Pruzanski, W.; Lambeau, Gérard; Lazdunski, Michel; Cho, W.; Kopilov, Julia; Kuksis, A.

doi:10.1016/j.bbalip.2006.11.008

Cited by 21 publications

(26 citation statements)

References 41 publications

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“…As indicated by the vast majority of lyso-PC produced (data not shown), hGIIF, hGIII, hGV, and hGX sPLA 2 s degraded much more PC than any other phospholipids from both LDL and HDL. This reflects the distribution of phospholipid classes in normal lipoproteins and is in accordance with previously published data (41,48,49). Lyso-PC species in hydrolyzed LDL and HDL were as follows: 16:0 Ͼ 18:0 Ͼ 18:1 Ͼ 18:2 for all four sPLA 2 s (data not shown).…”

Section: Falciparum-infectedsupporting

confidence: 76%

“…We previously demonstrated that the main mediators of parasite death by bee venom sPLA 2 -hydrolyzed VLDLs are PUFAs, especially AA, suggesting that the ability to produce PUFAs might be an important feature of the sPLA 2 anti-Plasmodium activity. It is known that hGX sPLA 2 preferentially hydrolyzes PC with polyenoic fatty acid species, including AA (41,42,(46)(47)(48), and that hGIIF sPLA 2 exhibits preference for PC species with AA (44), whereas hGV sPLA 2 preferentially attacks oligoenoic PL species and mostly releases saturated and monounsaturated fatty acids (41,42,(46)(47)(48). hGIII sPLA 2 did not seem to exhibit any PL preference (44).…”

Section: Discussionmentioning

confidence: 99%

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In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

et al. 2015

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We have previously shown that secreted phospholipases A 2 (sPLA 2 s) from animal venoms inhibit the in vitro development of Plasmodium falciparum, the agent of malaria. In addition, the inflammatory-type human group IIA (hGIIA) sPLA 2 circulates at high levels in the serum of malaria patients. However, the role of the different human sPLA 2 s in host defense against P. falciparum has not been investigated. We show here that 4 out of 10 human sPLA 2 s, namely, hGX, hGIIF, hGIII, and hGV, exhibit potent in vitro anti-Plasmodium properties with half-maximal inhibitory concentrations (IC 50 s) of 2.9 ؎ 2.4, 10.7 ؎ 2.1, 16.5 ؎ 9.7, and 94.2 ؎ 41.9 nM, respectively. Other human sPLA2s, including hGIIA, are inactive. The inhibition is dependent on sPLA 2 catalytic activity and primarily due to hydrolysis of plasma lipoproteins from the parasite culture. Accordingly, purified lipoproteins that have been prehydrolyzed by hGX, hGIIF, hGIII, and hGV are more toxic to P. falciparum than native lipoproteins. However, the total enzymatic activities of human sPLA 2 s on purified lipoproteins or plasma did not reflect their inhibitory activities on P. falciparum. For instance, hGIIF is 9-fold more toxic than hGV but releases a lower quantity of nonesterified fatty acids (NEFAs). Lipidomic analyses of released NEFAs from lipoproteins demonstrate that sPLA 2 s with anti-Plasmodium properties are those that release polyunsaturated fatty acids (PUFAs), with hGIIF being the most selective enzyme. NEFAs purified from lipoproteins hydrolyzed by hGIIF were more potent at inhibiting P. falciparum than those from hGV, and PUFA-enriched liposomes hydrolyzed by sPLA 2 s were highly toxic, demonstrating the critical role of PUFAs. The selectivity of sPLA 2 s toward lowand high-density (LDL and HDL, respectively) lipoproteins and their ability to directly attack parasitized erythrocytes further explain their anti-Plasmodium activity. Together, our findings indicate that 4 human sPLA 2 s are active against P. falciparum in vitro and pave the way to future investigations on their in vivo contribution in malaria pathophysiology.

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Section: Falciparum-infectedsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

et al. 2015

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“…How these sPLA2 isoforms exert such specific and opposite roles in atherosclerosis at the molecular level remains to be determined, but likely relies with their tissue and cell-specific expression, and their highly specific enzymatic properties on cells and lipoproteins. 22,48,49 Recently, a clinical trial testing the efficacy of A-002/varespladib, 20 a broadly specific inhibitor of sPLA2s GIIA, GV, and GX, 17 in patients with coronary artery disease was stopped for futility. 50 Our results may provide, at least in part, an explanation for the lack of efficacy of this inhibitor and clearly highlight the need for a specific targeting of individual sPLA2 enzymes with highly selective inhibitors that can discriminate between isoforms.…”

Section: Discussionmentioning

confidence: 99%

Group X Secreted Phospholipase A2 Limits the Development of Atherosclerosis in LDL Receptor–Null Mice

Ait‐Oufella

Herbin

Lahoute

et al. 2013

ATVB

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Objective-Several secreted phospholipases A2 (sPLA2s), including group IIA, III, V, and X, have been linked to the development of atherosclerosis, which led to the clinical testing of A-002 (varespladib), a broad sPLA2 inhibitor for the treatment of coronary artery disease. Group X sPLA2 (PLA2G10) has the most potent hydrolyzing activity toward phosphatidylcholine and is believed to play a proatherogenic role. Methods and Results-Here, we show that Ldlr -/-mice reconstituted with bone marrow from mouse group X-deficient mice (Pla2g10 -/-) unexpectedly display a doubling of plaque size compared with Pla2g10 +/+ chimeric mice. Macrophages of Pla2g10 -/-mice are more susceptible to apoptosis in vitro, which is associated with a 4-fold increase of plaque necrotic core in vivo. In addition, chimeric Pla2g10 -/-mice show exaggerated T lymphocyte (Th)1 immune response, associated with enhanced T-cell infiltration in atherosclerotic plaques. Interestingly, overexpression of human PLA2G10 in murine bone marrow cells leads to significant reduction of Th1 response and to 50% reduction of lesion size. Conclusion-PLA2G10

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“…This can increase extracellular deposition of cholesterol-rich modified lipoproteins [10]. In addition, sPLA 2 -V and sPLA 2 -X are able to hydrolyze phosphatidylcholine in high-density lipoprotein (HDL) with no oxidation or modification of apoA-I [11]. This modification of HDL by sPLA 2 impairs the capacity of HDL to promote cholesterol efflux from lipid-loaded macrophages, an effect that if present in vivo could contribute to intracellular lipid accumulation and foam cell formation, with impairment of the first step of the reverse cholesterol transport from arteries to the liver [12].…”

Section: Introductionmentioning

confidence: 99%

Role of secretory phospholipases in atherogenesis

Jönsson‐Rylander¹,

Lundin²,

Rosengren³

et al. 2008

Curr Atheroscler Rep

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Elevated circulating levels of secretory phospholipase A(2) (sPLA(2)) are associated with atherosclerotic cardiovascular disease. sPLA(2) can contribute to atherogenesis by hydrolyzing phospholipids of circulating lipoproteins and lipoproteins entrapped in the arterial wall and/or in cells that reside in the intima and that participate in the inflammatory response to lipoprotein deposition. This article reviews differences and similarities between sPLA(2)-IIA, sPLA(2)-V, and sPLA(2)-X, all of which are members of this family of enzymes with reported potential proatherogenic features. Published data suggest that each of the enzymes has a distinct profile characterized by differences in tissue expression and localization, capacity to act on phospholipids of cell membranes and lipoproteins, and their interaction with arterial proteoglycans. In addition, the article discusses results from the authors' laboratory showing that diet-induced or gene-induced hyperlipidemia in mice enhances the expression of sPLA(2)-V in different tissues, but not sPLA(2)-IIA. Such differences indicate that these enzymes may have different roles in atherosclerotic cardiovascular disease through their distinct profiles.

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Hydrolysis of minor glycerophospholipids of plasma lipoproteins by human group IIA, V and X secretory phospholipases A2

Cited by 21 publications

References 41 publications

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

Group X Secreted Phospholipase A2 Limits the Development of Atherosclerosis in LDL Receptor–Null Mice

Role of secretory phospholipases in atherogenesis

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Hydrolysis of minor glycerophospholipids of plasma lipoproteins by human group IIA, V and X secretory phospholipases A2

Cited by 21 publications

References 41 publications

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A 2

Group X Secreted Phospholipase A2 Limits the Development of Atherosclerosis in LDL Receptor–Null Mice

Role of secretory phospholipases in atherogenesis

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In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂

In Vitro Anti-Plasmodium falciparum Properties of the Full Set of Human Secreted Phospholipases A ₂