Microcystins: Biogenesis, Toxicity, Analysis, and Control

Schreidah, Celine M.; Ratnayake, Kasun; Senarath, Kanishka; Karunarathne, Ajith

doi:10.1021/acs.chemrestox.0c00164

Cited by 44 publications

(23 citation statements)

References 170 publications

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“…A strong interaction was found between MC-RR with the selenoprotein thioredoxin reductase TRXR1, which regulates the p53 activity and has a high metastatic potential [66,67]. Alteration of TRXR1 levels or activity is accompanied by pro-oxidative changes in the cell, inducing increased oxidative stress, and thus, damage to different biomolecules [66,68].…”

Section: Cellular Proliferation and Cancermentioning

confidence: 99%

Identification of Novel Molecular Targets of Four Microcystin Variants by High-Throughput Virtual Screening

et al. 2022

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Highly toxic microcystins (MCs) perform complex interactions with many proteins that induce cellular dysregulation, leading to the development of several diseases including cancer. There is significant diversity and chemical complexity among MC congeners, which makes it difficult to identify structure-dependent toxicity outcomes and their long-term effects. The aim of this study was to exploratory identify likely molecular targets of the main MC variants (MC-LA, MC-LR, MC-RR, and MC-LY) by conducting a computational binding affinity analysis using AutoDock Vina to evaluate the interaction of the toxins with 1000 proteins related to different biological functions. All four variants showed strong in silico interactions with proteins that regulate metabolism/immune system, CD38 (top scoring hit, −11.5 kcal/mol); inflammation, TLR4 (−11.4 kcal/mol) and TLR8 (−11.5 kcal/mol); neuronal conduction, BChE; renin–angiotensin signaling, (ACE); thyroid hormone homeostasis (TTR); and cancer-promoting processes, among other biochemical activities. The results show MCs have the potential to bind onto distinct molecular targets which could generate biochemical alterations through a number of signal transduction pathways. In short, this study broadens our knowledge about the mechanisms of action of different variants of microcystins and provides information for future direct experimentation.

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Section: Cellular Proliferation and Cancermentioning

confidence: 99%

Identification of Novel Molecular Targets of Four Microcystin Variants by High-Throughput Virtual Screening

et al. 2022

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“…Microcystins are hepatotoxins composed of a cyclic heptapeptide with more than 100 isoforms with different toxicities (Puddick, et al, 2014). Being produced by several genera of cyanobacteria, including Microcystis and Anabaena (Schreidah, et al, 2020). These toxins are considered to be very potent and widely distributed cyanotoxins, occurring worldwide.…”

Section: Microcystin and Oxidative Stressmentioning

confidence: 99%

Cellular oxidative stress stimulated by microcystin: review

Oliveira

Silva

2021

RSD

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Introduction: Cyanobacteria are organisms capable of producing a high number of bioactive molecules, known as cyanotoxins. Among the cyanotoxins, microcystins stand out, compounds with hepatotoxic potential. Studies claim that the most common and most toxic isoform among microcystins is microcystin-LR. One of the most frequently detected properties of microcystins is their ability to generate cellular oxidative stress. Thus, the present study is a bibliographic research about the biochemical mechanism of free radical generation caused by Microcystin LR. Methodology: for the preparation of this review, a survey was carried out in the national and international literature. The inclusion criteria for the construction of this work were original and review articles that addressed the ability of microcystin LR to generate oxidative damage. Results: Once they enter the body, microcystins accumulate in the liver, so that toxicity is associated with specific inhibition of protein phosphatase 1 and 2A (PP1 and PP2A), leading to disruption of cell integrity. Studies prove that MCs produce oxidative stress in vitro and in vivo and that they can act as tumor promoters. Conclusion: there is a possible relationship between cellular oxidative stress caused by microcystin. Thus, cyanobacterial blooms represent a threat to the health of several animals, including man, however, further studies on the topic addressed are needed.

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“…61 Previous studies have reported MC-LR altered expression of liver cytochrome P450 (e.g., CYP 2E1) in mice, suggesting a possible involvement of the enzyme with its metabolism. 62 Therefore, a metabolism activation package (MAP) was included in the hydra assay. MAP was standardized and consisted of 2.4 μg/mL mice hepatic microsomal cytochrome P450, 225 μM NADPH, and 25 μM MgCl 2 .…”

Section: Hydra Assaymentioning

confidence: 99%

Application of Edible Montmorillonite Clays for the Adsorption and Detoxification of Microcystin

Rivenbark

Gong

Wright

et al. 2021

ACS Appl. Bio Mater.

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Exposure to microcystins (MCs) in humans and animals commonly occurs through the consumption of drinking water and food contaminated with cyanobacteria. Although studies have focused on developing water filtration treatments for MCs using activated carbon, dietary sorbents to reduce the bioavailability of MCs from the stomach and intestines have not been reported. To address this need, edible calcium and sodium montmorillonite clays were characterized for their ability to bind MC containing leucine and arginine (MC-LR) under conditions simulating the gastrointestinal tract and compared with a medical-grade activated carbon. Results of in vitro adsorption isotherms and thermodynamics showed that binding plots for MC-LR on montmorillonites fit the Langmuir model with high binding capacity, affinity, Gibbs free energy, and enthalpy. The in silico results from molecular modeling predicted that the major binding mechanisms involved electrostatics and hydrogen bonds, and that interlayers were important binding sites. The safety and detoxification efficacy of the sorbents against MC-LR were validated in a battery of living organisms, including Hydra vulgaris, Lemna minor, and Caenorhabditis

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Microcystins: Biogenesis, Toxicity, Analysis, and Control

Cited by 44 publications

References 170 publications

Identification of Novel Molecular Targets of Four Microcystin Variants by High-Throughput Virtual Screening

Identification of Novel Molecular Targets of Four Microcystin Variants by High-Throughput Virtual Screening

Cellular oxidative stress stimulated by microcystin: review

Application of Edible Montmorillonite Clays for the Adsorption and Detoxification of Microcystin

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