NMR Structural Studies of Fumonisin B1 and Related Compounds from Fusarium moniliforme

Blackwell, Barbara A.; Edwards, O. E.; Fruchier, Alain; ApSimon, John W.; Miller, J. David

doi:10.1007/978-1-4899-1379-1_7

Cited by 48 publications

(51 citation statements)

References 27 publications

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“…6). In other studies (19), we have shown that 50 M FB 1 and AP 1 reduced cell number by 50 and 32%, respectively, after 24 h. 3 Therefore, PAP 1 appears to be considerably more toxic for HT29 cells than either of the parent fumonisin precursors.…”

Section: Inhibition Of Ceramide Synthase By Fumonisin Analogs-all Of mentioning

confidence: 61%

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Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase

Humpf¹,

Schmelz²,

Meredith³

et al. 1998

Journal of Biological Chemistry

142

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Fumonisin B 1 (FB 1 ) is the predominant member of a family of mycotoxins produced by Fusarium moniliforme (Sheldon) and related fungi. Certain foods also contain the aminopentol backbone (AP 1 ) that is formed upon base hydrolysis of the ester-linked tricarballylic acids of FB 1 . Both FB 1 and, to a lesser extent, AP 1 inhibit ceramide synthase due to structural similarities between fumonisins (as 1-deoxy-analogs of sphinganine) and sphingoid bases. To explore these structure-function relationships further, erythro-and threo-2-amino, 3-hydroxy-(and 3, 5-dihydroxy-) octadecanes were prepared by highly stereoselective syntheses. All of these analogs inhibit the acylation of sphingoid bases by ceramide synthase, and are themselves acylated with V max /K m of 40 -125 for the erythro-isomers (compared with approximately 250 for D-erythro-sphinganine) and 4 -6 for the threo-isomers. Ceramide synthase also acylates AP 1 (but not FB 1 , under the conditions tested) to N-palmitoyl-AP 1 (PAP 1 ) with a V max /K m of approximately 1. The toxicity of PAP 1 was evaluated using HT29 cells, a human colonic cell line. PAP 1 was at least 10 times more toxic than FB 1 or AP 1 and caused sphinganine accumulation as an inhibitor of ceramide synthase. These studies demonstrate that: the 1-hydroxyl group is not required for sphingoid bases to be acylated; both erythro-and threo-isomers are acylated with the highest apparent V max /K m for the erythro-analogs; and AP 1 is acylated to PAP 1 , a new category of ceramide synthase inhibitor as well as a toxic metabolite that may play a role in the diseases caused by fumonisins.Fumonisins are mycotoxins produced by Fusarium moniliforme (Sheldon) and related fungi that are common contaminants of maize and certain other foods (1). Fumonisin B 1 (FB 1 ) 1 is comprised of a long chain aminopentol (AP 1 ) with two of the side chain hydroxyls esterified to tricarballylic acids ( Fig. 1) (2, 3). Although numerous fumonisins have been characterized (1-4), FB 1 is usually the most abundant in contaminated food, except when corn has been treated with base to produce masa flour for tortillas, which hydrolyzes FB 1 to AP 1 (1).Fumonisins are responsible for at least two diseases, equine leukoencephalomalacia and porcine pulmonary edema (5, 6). Studies with these and other animals have uncovered a wide spectrum of toxicologic effects, which include hepatotoxicity, nephrotoxicity, neurotoxicity, developmental toxicity, and immunosuppression (and immunostimulation under some conditions) (for reviews, see Refs. 1, 7, and 8). Fumonisins are also hepatocarcinogenic in rats (1) and have been implicated in esophageal cancer in humans in South Africa and China (9 -11).The diverse effects of these mycotoxins appear to be due to inhibition of ceramide synthase, the enzyme that catalyzes the acylation of sphinganine, sphingosine, and other sphingoid bases (12, 13). Inhibition has been shown in vitro with intact cells and for animals exposed to fumonisins (7) and is manifested by up to several hundredfold incre...

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Section: Inhibition Of Ceramide Synthase By Fumonisin Analogs-all Of mentioning

confidence: 61%

“…1) (2,3). Although numerous fumonisins have been characterized (1)(2)(3)(4), FB 1 is usually the most abundant in contaminated food, except when corn has been treated with base to produce masa flour for tortillas, which hydrolyzes FB 1 to AP 1 (1).…”

mentioning

confidence: 99%

Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase

Humpf¹,

Schmelz²,

Meredith³

et al. 1998

Journal of Biological Chemistry

142

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“…This makes them difficult to study. Usually they are extracted in aqueous methanol or aqueous acetonitrile (20). High-performance liquid chromatography with fluorescent detection is the most widely used analytic method (202).…”

Section: Fumonisinsmentioning

confidence: 99%

Mycotoxins

2003

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Mycotoxins are secondary metabolites produced by microfungi that are capable of causing disease and death in humans and other animals. Because of their pharmacological activity, some mycotoxins or mycotoxin derivatives have found use as antibiotics, growth promotants, and other kinds of drugs; still others have been implicated as chemical warfare agents. This review focuses on the most important ones associated with human and veterinary diseases, including aflatoxin, citrinin, ergot akaloids, fumonisins, ochratoxin A, patulin, trichothecenes, and zearalenone

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“…These mycotoxins have a chemical structure similar to that of ceramides, and it has been shown that they interfere in the lipid metabolism of the cell (30,40). After isolation and characterization of fumonisin B1 (FB1) and FB2 from cultures of Fusarium verticillioides (F. monoliforme; Gibberella fujikuroi mating population A) strain MRC 826, an interest in these toxins has arisen (3).…”

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confidence: 99%

Immunobiological Effects of Fumonisin B1 in Experimental Subchronic Mycotoxicoses in Rats

Theumer

Camacho

Masih

et al. 2002

Clin Vaccine Immunol

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Fumonisin B1 (FB1), the principal secondary metabolite produced by the fungus Fusarium verticillioides (Gibberella fujikuroi mating population A), is a potent toxin that can be found in fungus-contaminated corn and corn-based food products. We have investigated the immunobiological effects of subchronic dietary exposure to FB1 in male Wistar rats. Animals were fed with diets containing 0 (control) or 100 ppm of FB1 for 12 weeks. The total FB1 intake on day 90 was 810 mg/kg of body weight. Food consumption, body weight, and body weight gain on day 90 were reduced in animals exposed to FB1. Histopathologic changes consisted of histiocytic perivascular infiltrate and an increased number of Kupffer cells in the liver, necrosis and apoptosis of tubular epithelial cells in the kidney, and increased mitotic figures and lymphocytic infiltrate in the small intestine. Serum enzyme alkaline phosphatase was significantly elevated in rats fed FB1, while triglyceride levels decreased compared to controls. Treatment with FB1 in vivo or in vitro did not have a significant effect on mitogen-induced proliferation of spleen mononuclear cells. However, increased levels of interleukin-4 (IL-4) and decreased levels of IL-10 were released by these cells in culture compared to controls. FB1 in vivo or in vitro decreased the hydrogen peroxide (H 2 O 2 ) released by peritoneal macrophages, while no changes in levels of superoxide anion produced by total peritoneal cells were detected. The results from the present work demonstrate that subchronic FB1 intake could affect the small intestine and alter the interleukin profile and some main functions of macrophages in antitumor activity.

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NMR Structural Studies of Fumonisin B1 and Related Compounds from Fusarium moniliforme

Cited by 48 publications

References 27 publications

Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase

Acylation of Naturally Occurring and Synthetic 1-Deoxysphinganines by Ceramide Synthase

Mycotoxins

Immunobiological Effects of Fumonisin B1 in Experimental Subchronic Mycotoxicoses in Rats

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