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Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.

ABSTRACT: Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala.FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same time as urine collection. In the first study, blood spots and urine were collected every 3 months (March 2011 to February 2012) from women living in low (Chimaltenango and Escuintla) and high (Jutiapa) FB exposure communities (1240 total recruits). The UFB1 , Sa 1-P/So 1-P ratio, and Sa 1-P/mL in blood spots were significantly higher in the high FB1 intake community compared to the low FB1 intake communities. The results were confirmed in a follow-up study (February 2013) involving 299 women living in low (Sacatepéquez) and high (Santa Rosa and Chiquimula) FB exposure communities.High levels of FB1 intake are correlated with changes in Sa 1-P and the Sa 1-P/So 1-P ratio in human blood in a manner consistent with FB1 inhibition of CerS.

SUBMITTER: Riley RT

PROVIDER: S-EPMC4956729 | biostudies-literature | 2015 Nov

REPOSITORIES: biostudies-literature

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Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.

Riley Ronald T RT Torres Olga O Matute Jorge J Gregory Simon G SG Ashley-Koch Allison E AE Showker Jency L JL Mitchell Trevor T Voss Kenneth A KA Maddox Joyce R JR Gelineau-van Waes Janee B JB

Molecular nutrition & food research 20150903 11

<h4>Scope</h4>Fumonisin (FB) occurs in maize and is an inhibitor of ceramide synthase (CerS). We determined the urinary FB1 (UFB1 ) and sphingoid base 1-phosphate levels in blood from women consuming maize in high and low FB exposure communities in Guatemala.<h4>Methods and results</h4>FB1 intake was estimated using the UFB1 . Sphinganine 1-phosphate (Sa 1-P), sphingosine 1-phosphate (So 1-P), and the Sa 1-P/So 1-P ratio were determined in blood spots collected on absorbent paper at the same tim ...[more]

PMID: 26264677

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Project description:Fumonisin (FB) mycotoxins produced by species of the genus Fusarium detrimentally affect human and animal health upon consumption, due to the inhibition of ceramide synthase. In the present work, we set out to identify mechanisms of self-protection employed by the FB1 producer Fusarium verticillioides FB1 biosynthesis was shown to be compartmentalized, and two cluster-encoded self-protection mechanisms were identified. First, the ATP-binding cassette transporter Fum19 acts as a repressor of the FUM gene cluster. Appropriately, FUM19 deletion and overexpression increased and decreased, respectively, the levels of intracellular and secreted FB1 Second, the cluster genes FUM17 and FUM18 were shown to be two of five ceramide synthase homologs in Fusarium verticillioides, grouping into the two clades CS-I and CS-II in a phylogenetic analysis. The ability of FUM18 to fully complement the yeast ceramide synthase null mutant LAG1/LAC1 demonstrated its functionality, while coexpression of FUM17 and CER3 partially complemented, likely via heterodimer formation. Cell viability assays revealed that Fum18 contributes to the fungal self-protection against FB1 and increases resistance by providing FUM cluster-encoded ceramide synthase activity.IMPORTANCE The biosynthesis of fungal natural products is highly regulated not only in terms of transcription and translation but also regarding the cellular localization of the biosynthetic pathway. In all eukaryotes, the endoplasmic reticulum (ER) is involved in the production of organelles, which are subject to cellular traffic or secretion. Here, we show that in Fusarium verticillioides, early steps in fumonisin production take place in the ER, together with ceramide biosynthesis, which is targeted by the mycotoxin. A first level of self-protection is given by the presence of a FUM cluster-encoded ceramide synthase, Fum18, hitherto uncharacterized. In addition, the final fumonisin biosynthetic step occurs in the cytosol and is thereby spatially separate from the fungal ceramide synthases. We suggest that these strategies help the fungus to avoid self-poisoning during mycotoxin production.

Project description:Previous research has demonstrated human exposure to mycotoxins among Guatemalans, with high levels of mycotoxins being found in blood and urine samples as well as in maize for human consumption. Mishandling of crops such as maize during pre- and post-harvest has been associated with mycotoxin contamination. The overarching goal of this study was to identify risk factors for aflatoxin and fumonisin exposure in Guatemala. A cross-sectional survey of 141 women tortilla makers was conducted in the departments of Guatemala, Sololá, Suchitepéquez, Izabal, and Zacapa in February 2022. Maize and tortilla samples were collected and analyzed for aflatoxin B1 (AFB1) and fumonisin B1, B2, and B3 contamination (FB1, FB2, FB3). Urine samples were collected and analyzed for urinary FB1 (uFB1) contamination. A questionnaire was administered to collect data on sociodemographic characteristics, dietary intake of maize-based foods the week prior to the study, and maize handling practices. Descriptive statistics were used to describe common maize handling practices. A univariable analysis was conducted to identify predictors of low/high AFB1, total fumonisins, and uFB1. Multivariable logistic regression was used to calculate adjusted odds ratios (ORs) and 95% confidence intervals (CIs). During tortilla processing, a reduction in the AFB1 and total fumonisin levels was observed. The presence of AFB1 in maize was associated with department and mean total fumonisin level in maize (OR: 1.705, 95% CI: 1.113-2.613). The department where the tortilleria was located was significantly associated with the presence of fumonisins in tortillas. Increased consumption of Tortrix was significantly associated with the presence of FB1 in urine (OR: 1.652, 95% CI: 1.072-2.546). Results of this study can be used in the development and implementation of supply chain management practices that mitigate mycotoxin production, reduce food waste and economic loss, and promote food security.

Dataset Information

Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.

Publications

Evidence for fumonisin inhibition of ceramide synthase in humans consuming maize-based foods and living in high exposure communities in Guatemala.

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