Enniatins A1 and B1 alter calcium homeostasis of neuronal cells leading to apoptotic death

Pérez-Fuentes, Nadia; Alvariño, Rebeca; Alfonso, Amparo; González-Jartı́n, Jesús M.; Gegunde, Sandra; Vieytes, Mercedes R.; Botana, Luís M.

doi:10.1016/j.fct.2022.113361

Cited by 11 publications

(23 citation statements)

References 31 publications

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“…Further work will also be required to determine the stage of the cell cycle that is disrupted by ENNA as well as evaluate if ENNA activates programmed cell death. The ENNA IC 50 identified for GC proliferation in the present study (i.e., 2 µM) is similar to toxicity assay IC 50 reported for other cell types including J774 macrophages [ 31 ], CHO-K1 cells [ 32 ], and neuroblastoma cells [ 33 ].…”

Section: Discussionsupporting

confidence: 84%

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

Chiminelli

Spicer

Maylem

et al. 2022

Toxins

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The emerging Fusarium mycotoxins enniatins (ENNs) have been the focus of new research because of their well-documented existence in various cereal and grain products. Research findings indicate that reproductive disorders may be caused by exposure to Fusarium mycotoxins, but little work has evaluated ENNs on reproductive function. Therefore, to determine the effects of ENNA on the proliferation and steroidogenesis of granulosa cells (GC), experiments were conducted using bovine GC cultures. In vitro, ENNA (1–5 μM) inhibited (p < 0.05) hormone-induced GC progesterone and estradiol production. The inhibitory effect of ENNA on estradiol production was more pronounced in small- than large-follicle GC. In large-follicle GC, 0.3 μM ENNA had no effect (p > 0.10) whereas 1 and 3 μM ENNA inhibited GC proliferation. In small-follicle GC, ENNA (1–5 μM) dramatically decreased (p < 0.05) GC proliferation. Using cell number data, the IC50 of ENNA was estimated at 2 μM for both follicle sizes. We conclude that ENNA can directly inhibit ovarian function in cattle, decreasing the proliferation and steroid production of GC.

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Section: Discussionsupporting

confidence: 84%

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

Chiminelli

Spicer

Maylem

et al. 2022

Toxins

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“…ENN A1 was found to have a calcium profile similar to Tg, suggesting that it may act on the same organelle as the SERCA inhibitor. 4 The first step in this study was to determine the effect of ENN B1 on calcium fluxes in the presence of Tg in order to elucidate its interaction with the cellular calcium regulation system. Cells were sequentially treated with 2 μM Tg and 5 μM ENN B1, concentrations that had previously shown pronounced effects on calcium fluxes in this cell line.…”

Section: Resultsmentioning

confidence: 99%

“…Cells were sequentially treated with 2 μM Tg and 5 μM ENN B1, concentrations that had previously shown pronounced effects on calcium fluxes in this cell line. 4,16 The percentage of variation in the cytosolic calcium was calculated across different segments. The percentage of reduction or increase in calcium release from reservoirs and calcium uptake was calculated by comparing the effects of the compounds alone to the effects of the compound mixture.…”

Section: Resultsmentioning

confidence: 99%

“…5 In SH-SY5Y cells, ENNs A1 and B1 did not affect MMP, and only ENN A1 increased ROS production. 3,4 Despite their widespread occurrence and cytotoxicity, the precise mechanism of action of ENNs remains unclear. Traditionally, ENNs have been identified as ionophores since it was proposed in 1973 that ENN B forms complexes on cell membranes, facilitating the passage of ions.…”

Section: Introductionmentioning

confidence: 99%

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Enniatins A1 and B1 Modulate Calcium Flux through Alternative Pathways beyond Mitochondria

Pérez-Fuentes,

Alvariño,

Alfonso

et al. 2024

J. Agric. Food Chem.

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Enniatins (ENNs) A1 and B1, previously considered ionophores, are emerging mycotoxins with effects on Ca 2+ homeostasis. However, their exact mechanism of action remains unclear. This study investigated how these toxins affect Ca 2+ flux in SH-SY5Y cells. ENN A1 induced Ca 2+ influx through store-operated channels (SOC). The mitochondrial uncoupler FCCP reduced this influx, suggesting that the mitochondrial status influences the toxin effect. Conversely, ENN B1 did not affect SOC but acted on another Ca 2+ channel, as shown when nickel, which directly blocks the Ca 2+ channel pore, is added. Mitochondrial function also influenced the effects of ENN B1, as treatment with FCCP reduced toxin-induced Ca 2+ depletion and uptake. In addition, both ENNs altered mitochondrial function by producing the opening of the mitochondrial permeability transition pore. This study describes for the first time that ENN A1 and B1 are not Ca 2+ ionophores and suggests a different mechanism of action for each toxin.

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“…Additionally, ENN B1 was recently reported to permeabilize the lysosomal membrane by destabilizing the LAMP-2 complex at a concentration close to the EC 50 (1.5–1.7 µmol/L) [ 39 ]. Moreover, a recent study highlighted the ability of ENN B1 to alter calcium homeostasis leading to apoptotic cell death in SH-SY5Y human neuroblastoma cells [ 40 ].…”

Section: Biological Characteristicsmentioning

confidence: 99%

Enniatin B1: Emerging Mycotoxin and Emerging Issues

Felice

Spicer

Caloni

2023

Toxins

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Although over the last 10 years several studies have focused on the emerging mycotoxins known as enniatins (ENNs), there is still a lack of knowledge regarding their toxicological effects and the development of a correct risk assessment. This is especially true for enniatin B1 (ENN B1), considered the younger sister of the widely studied enniatin B (ENN B). ENN B1 has been found in several food commodities and, as with other mycotoxins, presents antibacterial and antifungal properties. On the other hand, ENN B1 has shown cytotoxic activity, impairment of the cell cycle, the induction of oxidative stress, and changes in mitochondrial membrane permeabilization, as well as negative genotoxic and estrogenic effects. Overall, considering the paucity of information available regarding ENN B1, further studies are necessary to perform a risk assessment. This review summarizes information on the biological characteristics and toxicological effects of ENN B1 as well as the future challenges that this mycotoxin could present.

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Enniatins A1 and B1 alter calcium homeostasis of neuronal cells leading to apoptotic death

Cited by 11 publications

References 31 publications

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

In Vitro Effects of Enniatin A on Steroidogenesis and Proliferation of Bovine Granulosa Cells

Enniatins A1 and B1 Modulate Calcium Flux through Alternative Pathways beyond Mitochondria

Enniatin B1: Emerging Mycotoxin and Emerging Issues

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