Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity

Guillaume, Carole; Calzada, Catherine; Lagarde, Michel; Schrével, Joseph; Deregnaucourt, Christiane

doi:10.1194/jlr.m600111-jlr200

Cited by 26 publications

(20 citation statements)

References 55 publications

(70 reference statements)

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“…LA considerably inhibited the growth of P. falciparum in vitro, as well as of Plasmodium vinckei petteri and Plasmodium yoelii nigeriensis in mice; however, antioxidant compounds markedly decreased the fatty acid‐induced parasite killing effect (Krugliak et al, ; Kumaratilake, Robinson, Ferrante, & Poulos, ). Hence, LA may be expected to exert toxicity to cultured P. falciparum via extracellular production of linoleate peroxides/epoxides (Guillaume, Calzada, Lagarde, Schrevel, & Deregnaucourt, ). Additionally, antiplasmodium potential of phenolics and flavonoids in GSO would have to be addressed via malaria parasite metabolism and development (Alson et al, ; Cai, Zhang, Ji, & Xing, ; Kusch et al, ; Palaniswamy, Pradeep, Sathya, & Angayarkanni, ).…”

Section: Discussionmentioning

confidence: 99%

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Prommaban

Utama‐ang

Chaikitwattana

et al. 2019

Phytotherapy Research

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Guava (Psidium guajava) is a widely consumed fruit and has been commercialized in markets. The seeds are by-products of the processing procedures performed by the commercial guava juice industry. They are considered a nutritional resource that has been poorly utilized as they contain essential fatty acids such as linoleic acid (LA) and phenolics in abundance. In the study, guava seed oil (GSO) was used, which was obtained by hexane extraction of guava seeds to determine composition and test toxicity, cell migration, cancer cell viability, and plasmodium growth. GSO was found to be relatively nontoxic to normal hepatocytes and peripheral blood mononuclear cells, with mice for 14 days showing median lethal dose (LD 50 ) > 10 mg/kg and rats for up to 90 days. Surprisingly, the oil inhibited the proliferation of the human erythroleukemic cells in a dose-dependent manner with the half maximal inhibitory concentration values of 155 and 137 μg/ml at 24 and 48 hr, respectively. Importantly, GSO at 500 μg/ml was found to increase the degree of migration of keratinocytes (HaCaT). These observations suggest that edible P. guajava seed oil, which is abundant with linoleic acid and antioxidants, can promote skin wound healing and inhibit the proliferation of leukemic cells.

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Section: Discussionmentioning

confidence: 99%

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Prommaban

Utama‐ang

Chaikitwattana

et al. 2019

Phytotherapy Research

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“…The effect of phospholipase A 2 towards Plasmodium development has been extensively studied (Deregnaucourt & Scrével, 2000; Zieler et al ., 2001; Guillaume et al ., 2004), although the exact mechanism of action is not completely understood. In culture, PLA 2 s have an indirect effect by degrading lipoproteins present in serum, which in turn produce components (eg arachidonic, linoleic and docosahexaenoic acid) toxic to the parasite (Guillaume et al ., 2006).…”

Section: Discussionmentioning

confidence: 99%

Expression of a mutated phospholipase A₂ in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development

Rodrigues

Santos

Carvalho

et al. 2008

Insect Molecular Biology

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The genetic manipulation of mosquito vectors is an alternative strategy in the fight against malaria. It was previously shown that bee venom phospholipase A2 (PLA2) inhibits ookinete invasion of the mosquito midgut although mosquito fitness was reduced. To maintain the PLA2 blocking ability without compromising mosquito biology, we mutated the protein-coding sequence to inactivate the enzyme while maintaining the protein's structure. DNA encoding the mutated PLA2 (mPLA2) was placed downstream of a mosquito midgut-specific promoter (Anopheles gambiae peritrophin protein 1 promoter, AgPer1) and this construct used to transform Aedes fluviatilis mosquitoes. Four different transgenic lines were obtained and characterized and all lines significantly inhibited Plasmodium gallinaceum oocyst development (up to 68% fewer oocysts). No fitness cost was observed when this mosquito species expressed the mPLA2.

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“…We demonstrated that venom sPLA 2 s exert an indirect killing of P. falciparum through hydrolysis of human plasma phospholipids (PLs) present in the parasite culture medium (3,4). We also demonstrated that the enzymatic hydrolysis of human lipoproteins by bee venom sPLA 2 generates lipid products that are toxic to the parasite (6). Nonesterified fatty acids (NEFAs), especially polyunsaturated NEFAs (PUFAs), were identified as the main mediators of parasite death.…”

mentioning

confidence: 98%

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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Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity

Cited by 26 publications

References 55 publications

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Expression of a mutated phospholipase A₂ in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development

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

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Interplay between lipoproteins and bee venom phospholipase A2 in relation to their anti-plasmodium toxicity

Cited by 26 publications

References 55 publications

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Linoleic acid‐rich guava seed oil: Safety and bioactivity

Expression of a mutated phospholipase A2 in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development

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

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Product

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Expression of a mutated phospholipase A₂ in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development

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