Starvation and pH stress conditions induced mitochondrial dysfunction, ROS production and autophagy in Trypanosoma cruzi epimastigotes

Pedra-Rezende, Yasmin; Fernandes, Michelle Casal; Mesquita-Rodrigues, Camila; Stiebler, Renata; Bombaça, Ana Cristina S.; Pinho, Nathalia; Cuervo, Patrícia; Castro, Solange L. de; Menna-Barreto, Rubem F.S.

doi:10.1016/j.bbadis.2020.166028

Cited by 15 publications

(12 citation statements)

References 56 publications

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“…The succinate dehydrogenase complex (GO:0000104), which is located in the inner mitochondrial membrane and provides electrons for the mitochondrial aerobic and energy-producing respiratory chain of eukaryotic cells, was down-regulated at high oxalic acid concentrations ( Table S8 ) [ 36 ]. Mitochondrial dysfunction can also lead to excess production of ROS, thereby causing oxidative stress [ 37 ]. However, GO annotation found that the genes encoding ROS scavenging enzymes, such as glutathione peroxidase (GO:0004602) and catalase (GO:0004096) ( Tables S9 and S10 ), were significantly down-regulated at high oxalic acid concentrations [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Revealed the Mechanism of Inhibition of Saprophytic Growth of Sparassis latifolia by Excessive Oxalic Acid

Qiu

Wang

et al. 2022

Cells

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Sparassis latifolia, a highly valued edible fungus, is a crucial medicinal and food resource owing to its rich active ingredients and pharmacological effects. Excessive oxalic acid secreted on a pine-sawdust-dominated substrate inhibits its mycelial growth, and severely restricts the wider development of its cultivation. However, the mechanism underlying the relationship between oxalic acid and slow mycelial growth remains unclear. The present study reported the transcriptome-based response of S. latifolia induced by different oxalic acid concentrations. In total, 9206 differentially expressed genes were identified through comparisons of three groups; 4587 genes were down-regulated and 5109 were up-regulated. Transcriptome analysis revealed that excessive oxalic acid mainly down-regulates the expression of genes related to carbohydrate utilization pathways, energy metabolism, amino acid metabolism, protein synthesis metabolism, glycan biosynthesis, and signal transduction pathways. Moreover, genes encoding for wood-degrading enzymes were predominantly down-regulated in the mycelia treated with excessive oxalic acid. Taken together, the study results provide a speculative mechanism underlying the inhibition of saprophytic growth by excessive oxalic acid and a foundation for further research on the growth of S. latifolia mycelia.

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Section: Discussionmentioning

confidence: 99%

Transcriptome Analysis Revealed the Mechanism of Inhibition of Saprophytic Growth of Sparassis latifolia by Excessive Oxalic Acid

Qiu

Wang

et al. 2022

Cells

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“…Under acidic conditions, epimastigotes, the forms found in the vector, release membrane lipids [41]. Trypanosoma cruzi epimastigotes exhibit changes in morphology, especially in epimastigotes [42], which after 24 h induce large metabolic alterations [43]. However, it is still unclear how acidic conditions induce Journal of Immunology Research parasite changes over short periods.…”

Section: Discussionmentioning

confidence: 99%

Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

Vasconcelos

Andrade

Souza-Melo

et al. 2021

Journal of Immunology Research

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All extracellular forms of Trypanosoma cruzi, the causative agent of Chagas disease, release extracellular vesicles (EVs) containing major surface molecules of the parasite. EV release depends on several mechanisms (internal and external). However, most of the environmental conditions affecting this phenomenon are still unknown. In this work, we evaluated EV release under different stress conditions and their ability to be internalized by the parasites. In addition, we investigated whether the release conditions would affect their immunomodulatory properties in preactivated bone marrow-derived macrophages (BMDM). Sodium azide and methyl-cyclo-β-dextrin (CDB) reduced EV release, indicating that this phenomenon relies on membrane organization. EV release was increased at low temperatures (4°C) and acidic conditions (pH 5.0). Under this pH, trypomastigotes differentiated into amastigotes. EVs are rapidly liberated and reabsorbed by the trypomastigotes in a concentration-dependent manner. Nitrosative stress caused by sodium nitrite in acid medium or S-nitrosoglutathione also stimulated the secretion of EVs. EVs released under all stress conditions also maintained their proinflammatory activity and increased the expression of iNOS, Arg 1, IL-12, and IL-23 genes in IFN-γ and LPS preactivated BMDM. In conclusion, our results suggest a budding mechanism of release, dependent on the membrane structure and parasite integrity. Stress conditions did not affect functional properties of EVs during interaction with host cells. EV release variations under stress conditions may be a physiological response against environmental changes.

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“…Our group also demonstrated that alkaline medium led to early exacerbation of autophagy and mitochondrial impairment. These features recovered over time, indicating a survival mechanism to increase the autophagic flux for the removal of damaged structures ( Pedra-Rezende et al, 2021 ). Leishmania major promastigotes deficient in Atg5, which are not capable of forming autophagosomes, also presented a remarkable decrease in their virulence in vitro and in vivo .…”

Section: Autophagy In Protozoamentioning

confidence: 99%

Different Drugs, Same End: Ultrastructural Hallmarks of Autophagy in Pathogenic Protozoa

et al. 2022

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Protozoan parasites interact with a wide variety of organisms ranging from bacteria to humans, representing one of the most common causes of parasitic diseases and an important public health problem affecting hundreds of millions of people worldwide. The current treatment for these parasitic diseases remains unsatisfactory and, in some cases, very limited. Treatment limitations together with the increased resistance of the pathogens represent a challenge for the improvement of the patient’s quality of life. The continuous search for alternative preclinical drugs is mandatory, but the mechanisms of action of several of these compounds have not been described. Electron microscopy is a powerful tool for the identification of drug targets in almost all cellular models. Interestingly, ultrastructural analysis showed that several classes of antiparasitic compounds induced similar autophagic phenotypes in trypanosomatids, trichomonadids, and apicomplexan parasites as well as in Giardia intestinalis and Entamoeba spp. with the presence of an increased number of autophagosomes as well as remarkable endoplasmic reticulum profiles surrounding different organelles. Autophagy is a physiological process of eukaryotes that maintains homeostasis by the self-digestion of nonfunctional organelles and/or macromolecules, limiting redundant and damaged cellular components. Here, we focus on protozoan autophagy to subvert drug effects, discussing its importance for successful chemotherapy.

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Starvation and pH stress conditions induced mitochondrial dysfunction, ROS production and autophagy in Trypanosoma cruzi epimastigotes

Cited by 15 publications

References 56 publications

Transcriptome Analysis Revealed the Mechanism of Inhibition of Saprophytic Growth of Sparassis latifolia by Excessive Oxalic Acid

Transcriptome Analysis Revealed the Mechanism of Inhibition of Saprophytic Growth of Sparassis latifolia by Excessive Oxalic Acid

Stress Induces Release of Extracellular Vesicles by Trypanosoma cruzi Trypomastigotes

Different Drugs, Same End: Ultrastructural Hallmarks of Autophagy in Pathogenic Protozoa

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