Lysophosphatidylcholine triggers cell differentiation in the protozoan parasite Herpetomonas samuelpessoai through the CK2 pathway

Dutra, Fernando L.; Vieira, Danielle P.; Coelho, Felipe Soares; Adade, Camila M.; Atella, Geórgia C.; Neto, Mario A. C. S.; Lopes, Angela H.

doi:10.2478/s11686-019-00135-8

Cited by 5 publications

(2 citation statements)

References 57 publications

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“…The current study indicated that C16:0 PAF and C18:1 LPC stimulate the differentiation of T. cruzi from epimastigotes to metacyclic trypomastigotes in vitro. This effect was abolished in the presence of WEB 2086, which has already been shown for a few trypanosomatids (Dutra et al., 1998, 2001a, 2001b, 2009, 2020; Gazos‐Lopes et al., 2014; Rodrigues et al., 1999; Silva‐Neto et al., 2002). In addition, the parasites heterozygous for TcPAQR did not respond to either C18:1 LPC or C16:0 PAF.…”

Section: Discussionsupporting

confidence: 65%

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

Coelho

Oliveira

Vieira

et al. 2021

Molecular Microbiology

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The lipid mediators, platelet‐activating factor (PAF) and lysophosphatidylcholine (LPC), play relevant pathophysiological roles in Trypanosoma cruzi infection. Several species of LPC, including C18:1 LPC, which mimics the effects of PAF, are synthesized by T. cruzi. The present study identified a receptor in T. cruzi, which was predicted to bind to PAF, and found it to be homologous to members of the progestin and adiponectin family of receptors (PAQRs). We constructed a three‐dimensional model of the T. cruzi PAQR (TcPAQR) and performed molecular docking to predict the interactions of the TcPAQR model with C16:0 PAF and C18:1 LPC. We knocked out T. cruzi PAQR (TcPAQR) gene and confirmed the identity of the expressed protein through immunoblotting and immunofluorescence assays using an anti‐human PAQR antibody. Wild‐type and knockout (KO) parasites were also used to investigate the in vitro cell differentiation and interactions with peritoneal mouse macrophages; TcPAQR KO parasites were unable to react to C16:0 PAF or C18:1 LPC. Our data are highly suggestive that PAF and LPC act through TcPAQR in T. cruzi, triggering its cellular differentiation and ability to infect macrophages.

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Section: Discussionsupporting

confidence: 65%

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

Coelho

Oliveira

Vieira

et al. 2021

Molecular Microbiology

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“…The present study showed that OA downregulated the mRNA and protein levels of FAS and sPLA 2 in SHRs. The enzyme sPLA 2 catalyzes the conversion of PC into lysoPC ( 104 ). FAS is involved in de novo lipogenesis by converting acetyl-coenzyme A into palmitate, which is subsequently esterified into TGs in the liver ( 105 ).…”

Section: Discussionmentioning

confidence: 99%

Antihypertensive activity of oleanolic acid is mediated via downregulation of secretory phospholipase A2 and fatty acid synthase in spontaneously hypertensive rats

et al. 2020

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Oleanolic acid (OA) is reported to possess antihypertensive activity via the regulation of lipid metabolism; however, the mechanisms underlying lipid regulation by OA are yet to be fully elucidated. The aim of the present study was to evaluate the mechanisms via which OA regulates lipid metabolism in spontaneously hypertensive rats (SHRs) via ultra-performance liquid chromatography-quadrupole/Orbitrap-mass spectrometry (MS)-based lipidomics analysis. SHRs were treated with OA (1.08 mg/kg) for 4 weeks. The liver tissues were excised, homogenized in dichloromethane and centrifuged, and subsequently the supernatant layer was collected and concentrated under vacuum to dryness. The dichloromethane extract was subjected to MS analysis and database searching, and comparison of standards was performed to identify potential biomarkers. Partial least squares-discriminant analysis performed on the liver lipidome revealed a total of 14 endogenous metabolites that were significantly changed in the SHR model group (SH group) compared with Wistar Kyoto rats [normal control (NC group)], including glycerophospholipids, sphingolipids and glycerides. Heatmaps revealed that the liver lipid profiles in the OA group were clustered more closely compared with those observed in the NC group, indicating that the antihypertensive effect of OA was mediated via regulation of liver lipid metabolites. It was observed that the protein levels of secretory phospholipase A 2 (sPLA 2 ) and fatty acid synthase (FAS) were increased in the SH group compared with the NC group. In addition, the levels of lysophosphatidylcholine and triglycerides in the liver were elevated, whereas the levels of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol were reduced in the SH group. Upon treatment with OA, the mRNA and protein levels of PLA 2 and FAS were observed to be downregulated. Collectively, the present study indicated that the antihypertensive activity of OA was mediated via downregulation of sPLA 2 and FAS in SHRs, and that treatment with OA resulted in significant improvements in blood pressure and associated abnormalities in the lipid metabolites.

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Influence of CK2 protein kinase activity on the interaction between Trypanosoma cruzi and its vertebrate and invertebrate hosts

de Oliveira Souza,

Gomes,

Lima

et al. 2024

Parasitol Res

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Lysophosphatidylcholine triggers cell differentiation in the protozoan parasite Herpetomonas samuelpessoai through the CK2 pathway

Cited by 5 publications

References 57 publications

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

A novel receptor for platelet‐activating factor and lysophosphatidylcholine in Trypanosoma cruzi

Antihypertensive activity of oleanolic acid is mediated via downregulation of secretory phospholipase A2 and fatty acid synthase in spontaneously hypertensive rats

Influence of CK2 protein kinase activity on the interaction between Trypanosoma cruzi and its vertebrate and invertebrate hosts

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