Identification of fumonisin B1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies

Jenkins, Gail; Tolleson, William H.; Newkirk, D. Keith; Roberts, Dean W.; Rowland, Kenneth L.; Saheki, Takeyori; Kobayashi, Kazuo; Howard, Paul C.; Melchoir, William B.

doi:10.1002/1099-0461(2000)14:6<320::aid-jbt4>3.0.co;2-9

Cited by 13 publications

(5 citation statements)

References 29 publications

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“…It has been demonstrated that fumonisin B 1 (FB1) disrupts sphingolipid metabolism by inhibiting sphingosine N-acyltransferase (ceramide synthase) in rat liver microsomes (Wang et al 1991). Fumonisin B 1 also inhibits other intracellular enzymes including protein phosphatase and arginosuccinate synthase (Jenkins et al 2000). Therefore, the cytotoxicity of FB1 exerts its toxicity by its ability to inhibit sphingolipid metabolism, protein metabolism, and the urea cycle.…”

Section: Introductioncontrasting

confidence: 70%

The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay

et al. 2009

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Lymphocytes cell obtained from healthy human donors and pigs were exposed to fumonisin B1 (FB1) and ochratoxin A (OTA), which have been found to be immunosuppressive, carcinogenic and mutagenic, to ascertain their single and combined cytotoxic effects with time and to assess the suitability of animal lymphocytes as test agents in comparison to human cells. The main objectives of this work were to assess the use of animal lymphocytes, particularly pig lymphocytes, for their use in the Methyl Thiazol Tetrazolium (MTT) cytotoxicity test, making them more accessible to animal research-based institutes in comparison to human lymphocytes previously used, and to study the cytotoxic and synergism or antagonistic effects of FB1 and OTA. The MTT assay, which measures cell viability and proliferation based on reduction of MTT to a blue dye, also used the addition of phytohaemagglutinin (PHA) to stimulate the blood cells. The results showed a progressive decrease in lymphocytes viability with time of exposure to the toxins. It was also noted that FB1, as compared to OTA, had a lower cytotoxicity on both human and pig lymphocytes cells. In addition, when the two mycotoxins were combined, a synergistic decrease of cell viability in both human and pig lymphocytes was observed, with pig lymphocytes showing a greater sensitivity. This study has shown that the MTT assay can be used for the determination of cytotoxicity of mycotoxins using animal, and in particular pig, lymphocytes, which eliminates the use of human donors and other cell cultures.

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Section: Introductioncontrasting

confidence: 70%

The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay

et al. 2009

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“…Along with its capability to disturb the metabolism of sphingolipids, fumonisin B1 has been reported to inhibit the mitochondrial electron transport chain complex I and encourage reactive oxygen species (ROS) generation, lipid peroxidation, and oxidative stress [117]. Additionally, fumonisin B1 was reported to have an inhibitory effect on argininosuccinate synthetase, a urea cycle enzyme that is responsible for catalyzing argininosuccinic acid formation from aspartate and citrulline [125].…”

Section: Fumonisinsmentioning

confidence: 99%

“…(d) Ionophore activity: Beauvericin and enniatins that are produced by species of Fusarium have ionophoric activities specific to potassium and cause an influx of potassium into the matrix of the mitochondria followed by swelling of the mitochondria [201]. (e) Metabolic enzyme inhibition: OTA, citroviridin, and AFB1 affect the metabolism of carbohydrates, while rubratoxin B and trichothecenes interfere with the metabolism of lipids [117,125]. The checmical structure of fumonisins has a high similarity to those of sphinganine and sphingosine, the sphingolipid backbones.…”

Section: Action Mechanisms Of Mycotoxins: Key Aspectsmentioning

confidence: 99%

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Mycotoxins Affecting Animals, Foods, Humans, and Plants: Types, Occurrence, Toxicities, Action Mechanisms, Prevention, and Detoxification Strategies—A Revisit

Awuchi

Ondari

Ogbonna

et al. 2021

Foods

187

100

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Mycotoxins are produced by fungi and are known to be toxic to humans and animals. Common mycotoxins include aflatoxins, ochratoxins, zearalenone, patulin, sterigmatocystin, citrinin, ergot alkaloids, deoxynivalenol, fumonisins, trichothecenes, Alternaria toxins, tremorgenic mycotoxins, fusarins, 3-nitropropionic acid, cyclochlorotine, sporidesmin, etc. These mycotoxins can pose several health risks to both animals and humans, including death. As several mycotoxins simultaneously occur in nature, especially in foods and feeds, the detoxification and/or total removal of mycotoxins remains challenging. Moreover, given that the volume of scientific literature regarding mycotoxins is steadily on the rise, there is need for continuous synthesis of the body of knowledge. To supplement existing information, knowledge of mycotoxins affecting animals, foods, humans, and plants, with more focus on types, toxicity, and prevention measures, including strategies employed in detoxification and removal, were revisited in this work. Our synthesis revealed that mycotoxin decontamination, control, and detoxification strategies cut across pre-and post-harvest preventive measures. In particular, pre-harvest measures can include good agricultural practices, fertilization/irrigation, crop rotation, using resistant varieties of crops, avoiding insect damage, early harvesting, maintaining adequate humidity, and removing debris from the preceding harvests. On the other hand, post-harvest measures can include processing, chemical, biological, and physical measures. Additionally, chemical-based methods and other emerging strategies for mycotoxin detoxification can involve the usage of chitosan, ozone, nanoparticles, and plant extracts.

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“…doi: 10.14252/foodsafetyfscj.2017004 400, 500 and 3000 μM for PP5, PP2Cα, PP2A, PP1γ2 and PP2B, respectively 8) . FB1 is also reported to interact with arginosuccinate synthase, a urea cycle enzyme 9) . Wide ranges of food contamination and distinct toxicity targets in different animal species of this toxicant continue to attract attentions of regulatory authorities as well as academic researchers [10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Possible Role of Phosphatidylcholine and Sphingomyelin on Fumonisin B1-mediated Toxicity

2017

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A major corn-related mycotoxin, fumonisin B1 (FB1), continues to attract attention of researchers as well as risk-assessors due to the diverse toxicological characteristics, including distinct target tissues in different animal species and opposite susceptibility in males and females in mice and rats. More than thirty years passed since the structure identification as a sphingoid-like chemical, but the causal mechanism of the toxicity remains obscure in spites of extensive studies. Considerable amounts of knowledge have been accumulated on the biochemical/toxicological actions of FB1, but the influence on lipid dynamics and mobilization in the body has not been focused well in relation to the FB1-mediated toxicity. Considerable influences of this toxin on mobilization of sphingolipids and phospholipids and also on adaptive changes in their compositions in tissues are implicated from recent studies on FB1-interacting ceramide synthases. Accumulated patho-physiological data also suggest a possible role of hepatic phospholipid on FB1-mediated toxicity. Thus, a mechanism of FB1-mediated toxicity is discussed in relation to the mobilization of phospholipids and sphingolipids in the body in this context.

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Identification of fumonisin B1 as an inhibitor of argininosuccinate synthetase using fumonisin affinity chromatography and in vitro kinetic studies

Cited by 13 publications

References 29 publications

The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay

The cytotoxic effect of fumonisin B1 and ochratoxin A on human and pig lymphocytes using the Methyl Thiazol Tetrazolium (MTT) assay

Mycotoxins Affecting Animals, Foods, Humans, and Plants: Types, Occurrence, Toxicities, Action Mechanisms, Prevention, and Detoxification Strategies—A Revisit

Possible Role of Phosphatidylcholine and Sphingomyelin on Fumonisin B1-mediated Toxicity

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