The effects of endoplasmic reticulum stressors, tunicamycin and dithiothreitol on Trypanosoma cruzi

Sandes, Jana Messias; Moura, Danielle Maria Nascimento; Santiago, Moana Divina da Silva; Lima, Gustavo Barbosa de; Filho, Paulo E. Cabral; Albuquerque, Suênia da Cunha Gonçalves de; Paiva-Cavalcanti, Milena de; Fontes, Adriana; Figueiredo, Regina Célia Bressan Queiroz de

doi:10.1016/j.yexcr.2019.111560

Cited by 10 publications

(3 citation statements)

References 60 publications

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“…It has been proved that DTT inhibits the activity of the plasmalemmal BK Ca channel, which means that under reduced conditions the potassium current does not flow through the channel [ 65 ]. It is also worth mentioning that the effect of DTT applied to whole cells leads to the depolarization of the IMM and an increase in the synthesis of ROS [ 66 ]. It is known that ROS are mainly formed in the mitochondria [ 67 ] as well as the high levels of ROS can lead to mitochondrial dysfunction [ 68 , 69 ].…”

Section: Discussionmentioning

confidence: 99%

Luteolin-Induced Activation of Mitochondrial BKCa Channels: Undisclosed Mechanism of Cytoprotection

et al. 2022

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Luteolin (LUT) is a well-known flavonoid that exhibits a number of beneficial properties. Among these, it shows cardioprotective effects, as confirmed by numerous studies. However, its effect on mitochondrial potassium channels, the activation of which is related to cytoprotection, as well as on heart ischemia/reperfusion (I/R) damage prevention, has not yet been investigated. The large conductance calcium-regulated potassium channel (mitoBKCa) has been identified in both the mitochondria of the vascular endothelial cells, which plays a significant role in the functioning of the cardiovascular system under oxidative stress-related conditions, and in the mitochondria of cardiomyocytes, where it is deeply involved in cardiac protection against I/R injury. Therefore, the aim of this study was to explore the role of the mitoBKCa channel in luteolin-induced cytoprotection. A number of in vitro, in vivo, ex vivo and in silico studies have confirmed that luteolin activates this channel in the mitochondria of cardiomyocytes and endothelial cells, which in turn leads to the protection of the endothelium and a significant reduction in the extent of damage resulting from myocardial infarction, where this effect was partially abolished by the mitoBKCa channel blocker paxilline. In conclusion, these results suggest that luteolin has cardioprotective effects, at least in part, through the activation of the mitoBKCa channel, shedding light on a new putative mechanism of action.

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Section: Discussionmentioning

confidence: 99%

Luteolin-Induced Activation of Mitochondrial BKCa Channels: Undisclosed Mechanism of Cytoprotection

et al. 2022

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“…However, some studies suggest that DTT may induce apoptosis by generating hydrogen peroxide and oxidative stress ( Held et al, 1996 ; Held and Melder, 1987 ). Similarly, several other DTT-mediated phenotypes are shown to be independent of ER stress ( Guillemette et al, 2007 ; MacKenzie et al, 2005 ; Messias Sandes et al, 2019 ; Tartier et al, 2000 ). Therefore, how DTT impacts cellular physiology remains to be fully understood.…”

Section: Introductionmentioning

confidence: 90%

Dithiothreitol causes toxicity in C. elegans by modulating the methionine–homocysteine cycle

Gokul

Singh

2022

eLife

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The redox reagent dithiothreitol (DTT) causes stress in the endoplasmic reticulum (ER) by disrupting its oxidative protein folding environment, which results in the accumulation and misfolding of the newly synthesized proteins. DTT may potentially impact cellular physiology by ER-independent mechanisms; however, such mechanisms remain poorly characterized. Using the nematode model Caenorhabditis elegans, here we show that DTT toxicity is modulated by the bacterial diet. Specifically, the dietary component vitamin B12 alleviates DTT toxicity in a methionine synthase-dependent manner. Using a forward genetic screen, we discover that loss-of-function of R08E5.3, an S-adenosylmethionine (SAM)-dependent methyltransferase, confers DTT resistance. DTT upregulates R08E5.3 expression and modulates the activity of the methionine-homocysteine cycle. Employing genetic and biochemical studies, we establish that DTT toxicity is a result of the depletion of SAM. Finally, we show that a functional IRE-1/XBP-1 unfolded protein response pathway is required to counteract toxicity at high, but not low, DTT concentrations.

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“… Goldshmidt et al (2010) reported that the expression of Bip of T. brucei was increased in both procyclic and blood stream forms in DTT-induced ER stress, and irrecoverable ER stress could induce spliced leader RNA silencing pathway (SLS pathway, a unique process in T. brucei ), which may accelerate programmed cell death (PCD). Besides, Messias Sandes et al (2019) showed that both DTT and tunicamycin could induce PCD in T. cruzi .…”

Section: The Upr In Parasites Suggests Potential Drug Targets For Inhibiting the Survival And Development Of Parasitesmentioning

confidence: 99%

Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis

Peng

Fang

et al. 2021

Front. Microbiol.

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Endoplasmic reticulum stress (ER stress) can be induced when cellular protein homeostasis is damaged, and cells can activate the unfolded protein response (UPR) to restore protein homeostasis or induce cell death to facilitate the survival of the whole system. Globally, parasites are a constant threat to human health and are therefore considered a serious public health problem. Parasitic infection can cause ER stress in host cells, and parasites also possess part or all of the UPR under ER stress conditions. In this review, we aim to clarify the role of ER stress pathways and related molecules in parasites for their survival and development, the pathogenesis of parasitosis in hosts, and the artemisinin resistance of Plasmodium, which provides some potential drug design targets to inhibit survival of parasites, relieves pathological damage of parasitosis, and solves the problem of artemisinin resistance.

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The effects of endoplasmic reticulum stressors, tunicamycin and dithiothreitol on Trypanosoma cruzi

Cited by 10 publications

References 60 publications

Luteolin-Induced Activation of Mitochondrial BKCa Channels: Undisclosed Mechanism of Cytoprotection

Luteolin-Induced Activation of Mitochondrial BKCa Channels: Undisclosed Mechanism of Cytoprotection

Dithiothreitol causes toxicity in C. elegans by modulating the methionine–homocysteine cycle

Endoplasmic Reticulum Stress, a Target for Drug Design and Drug Resistance in Parasitosis

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