Lipid metabolism in Trypanosoma cruzi: A review

Booth, Leigh-Ann; Smith, Terry

doi:10.1016/j.molbiopara.2020.111324

Cited by 20 publications

(34 citation statements)

References 244 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This gene encodes an adipose-specific phospholipase whose expression has been reported to be reduced in patients with peripheral artery disease, which is a common affection in patients with coronary artery disease [39,40]. Thus, as mentioned for PLCB3, the role of the phospholipases during T. cruzi infection has been widely studied as part of the lipid metabolism [41]. Nevertheless, although this phospholipase seems to be related with other cardiovascular traits and exhibit higher expression in heart tissue, its potential relation with Chagas disease remains to be determined.…”

Section: Box Plots Of Three Of the Most Interesting Genes Comparing Dnam Levels Between Chronic Chagas Cardiomyopathy Patients (Ccc) And mentioning

confidence: 99%

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

et al. 2021

View full text Add to dashboard Cite

A recent genome-wide association study (GWAS) identified a locus in chromosome 11 associated with the chronic cardiac form of Chagas disease. Here we aimed to elucidate the potential functional mechanism underlying this genetic association by analyzing the correlation among single nucleotide polymorphisms (SNPs) and DNA methylation (DNAm) levels as cis methylation quantitative trait loci (cis-mQTL) within this region. A total of 2,611 SNPs were tested against 2,647 DNAm sites, in a subset of 37 chronic Chagas cardiomyopathy patients and 20 asymptomatic individuals from the GWAS. We identified 6,958 significant cis-mQTLs (False Discovery Rate [FDR]<0.05) at 1 Mb each side of the GWAS leading variant, where six of them potentially modulate the expression of the SAC3D1 gene, the reported gene in the previous GWAS. In addition, a total of 268 cis-mQTLs showed differential methylation between chronic Chagas cardiomyopathy patients and asymptomatic individuals. The most significant cis-mQTLs mapped in the gene bodies of POLA2 (FDR = 1.04x10-11), PLAAT3 (FDR = 7.22x10-03), and CCDC88B (FDR = 1.89x10-02) that have been associated with cardiovascular and hematological traits in previous studies. One of the most relevant interactions correlated with hypermethylation of CCDC88B. This gene is involved in the inflammatory response, and its methylation and expression levels have been previously reported in Chagas cardiomyopathy. Our findings support the functional relevance of the previously associated genomic region, highlighting the regulation of novel genes that could play a role in the chronic cardiac form of the disease.

show abstract

Section: Box Plots Of Three Of the Most Interesting Genes Comparing Dnam Levels Between Chronic Chagas Cardiomyopathy Patients (Ccc) And mentioning

confidence: 99%

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

et al. 2021

View full text Add to dashboard Cite

show abstract

“…We also found that the sphingolipid metabolism pathway is enriched in the TcY-L1/2 −/− membrane subproteome from the upregulated proteins ( Supplementary Table S3 ), therefore, indicating that this pathway was likely enriched in TcY-L1/2 −/− trypomastigotes in comparison to the TcY-WT trypomastigotes. We did not find upregulated proteins that would relate directly to the sphingolipid metabolism pathway ( Booth and Smith, 2020 ). However, T. cruzi synthesizes the inositolphosphorylceramide as its primary phosphosphingolipid, which is also an attached lipid of GPI anchors ( McConville and Ferguson, 1993 ; Lester and Dickson, 1993 ; Bertello et al., 1995 ; Uhrig et al., 1996 ; Figueiredo et al., 2005 ).…”

Section: Discussionmentioning

confidence: 77%

“…The pathway enrichment analysis also revealed three pathways enriched for TcY-L2 −/− trypomastigotes in comparison to the TcY-WT trypomastigotes ( Supplementary Table 3 ), one from the down regulated proteins list (ether lipid metabolism) and two from the up regulated proteins list (arginine and proline metabolism and, diterpenoid biosynthesis). The ether lipid synthesis has not been fully studied yet and many related proteins are still to be characterized in T. cruzi ( Booth and Smith, 2020 ). The amino acid proline has been demonstrated to be involved in several essential aspects of T. cruzi ’s life cycle, such as differentiation of epimastigotes into metacyclic trypomastigotes and among intracellular stages, host cell invasion, and survival to thermal and nutritional stress ( Tonelli et al., 2004 ; Martins et al., 2009 ; Paes et al., 2013 ).…”

Section: Discussionmentioning

confidence: 99%

Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment

Oliveira

Rezende

Gorshkov

et al. 2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Trypanosoma cruzi invades non-professional phagocytic cells by subverting their membrane repair process, which is dependent on membrane injury and cell signaling, intracellular calcium increase, and lysosome recruitment. Cells lacking lysosome-associated membrane proteins 1 and 2 (LAMP1 and LAMP2) are less permissive to parasite invasion but more prone to parasite intracellular multiplication. Several passages through a different intracellular environment can significantly change T. cruzi’s gene expression profile. Here, we evaluated whether one single passage through LAMP-deficient (KO) or wild-type (WT) fibroblasts, thus different intracellular environments, could influence T. cruzi Y strain trypomastigotes’ ability to invade L6 myoblasts and WT fibroblasts host cells. Parasites released from LAMP2 KO cells (TcY-L2−/−) showed higher invasion, calcium signaling, and membrane injury rates, for the assays in L6 myoblasts, when compared to those released from WT (TcY-WT) or LAMP1/2 KO cells (TcY-L1/2−/−). On the other hand, TcY-L1/2−/− showed higher invasion, calcium signaling, and cell membrane injury rates, for the assays in WT fibroblasts, compared to TcY-WT and TcY-L1/2−/−. Albeit TcY-WT presented an intermediary invasion and calcium signaling rates, compared to the others, in WT fibroblasts, they induced lower levels of injury, which reinforces that signals mediated by surface membrane protein interactions also have a significant contribution to trigger host cell calcium signals. These results clearly show that parasites released from WT or LAMP KO cells are distinct from each other. Additionally, these parasites’ ability to invade the cell may be distinct depending on which cell type they interact with. Since these alterations most likely would reflect differences among parasite surface molecules, we also evaluated their proteome. We identified few protein complexes, membrane, and secreted proteins regulated in our dataset. Among those are some members of MASP, mucins, trans-sialidases, and gp63 proteins family, which are known to play an important role during parasite infection and could correlate to TcY-WT, TcY-L1/2−/−, and TcY-L2−/− biological behavior.

show abstract

“…That binding would be required to maintain the parasite flagellum in an extended stage in intermediate forms [40], as part of the rearrangement that the subpellicular array of trypanosomes undergoes in morphological transitions [44]. In addition, PA could act as precursor of CDP-DAG, required to complete the PI cycle [45].…”

Section: Discussionmentioning

confidence: 99%

Calcium Signaling Involves Na+/H+ Exchanger and IP3 Receptor Activation in T. cruzi Epimastigotes

et al. 2021

View full text Add to dashboard Cite

The calcium ion (Ca2+) plays a fundamental role in the metabolism and cell physiology of eukaryotic cells. In general, increases in cytosolic Ca2+ may come from both of the extracellular environment through specific channels and/or calcium release from intracellular stores. The mechanism by which the ion calcium (Ca2+) is released from intracellular stores in higher eukaryotes is well known; however, in lower eukaryotes is still a subject of study. In the present work, it was elucidated that Trypanosoma cruzi epimastigotes can release Ca2+ from intracellular stores in response to high osmolarity, in a process involving a protein kinase-regulated Na+/H+ exchanger present in the acidocalsisomes of the parasite. In addition, we demonstrated that epimastigote membranes are able to release Ca2+ in response to exogenous activators of both inositol 1,4,5-triphosphate (IP3) and Ryanodine receptors. Furthermore, we also summarize the involvement of calcium-related signaling pathways in biochemical and morphological changes triggered by hyperosmotic stress in T. cruzi epimastigotes.

show abstract

Lipid metabolism in Trypanosoma cruzi: A review

Cited by 20 publications

References 244 publications

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

GWAS loci associated with Chagas cardiomyopathy influences DNA methylation levels

Biological and Molecular Effects of Trypanosoma cruzi Residence in a LAMP-Deficient Intracellular Environment

Calcium Signaling Involves Na+/H+ Exchanger and IP3 Receptor Activation in T. cruzi Epimastigotes

Contact Info

Product

Resources

About