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Keywords = 2-amino-14,16-dimethyloctadecan

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19 pages, 2298 KB  
Article
The Emerging Mycotoxin 2-Amino-14, 16-Dimethyloctadecan-3-ol (AOD) Alters Transcriptional Regulation and Sphingolipid Metabolism and Undergoes N-Acylation by HepG2 Cells
by Shenlong Mo, Zhenying Hu, Huaiyi Zhu, Boming Yu, Xiaoyan Chen, Yu Chen, Alfred H. Merrill and Jingjing Duan
Toxins 2025, 17(8), 413; https://doi.org/10.3390/toxins17080413 - 15 Aug 2025
Cited by 2 | Viewed by 1351
Abstract
2-Amino-14,16-dimethyloctadecan-3-ol (AOD) is commonly found in foods contaminated with Fusarium avenaceum, particularly cereals or fruits, and is structurally related to Fusarium mycotoxins (fumonisins) and mammalian sphingoid bases, especially 1-deoxysphinganine (m18:0); therefore, it might enter systemic circulation and tissues upon dietary intake. Knowledge [...] Read more.
2-Amino-14,16-dimethyloctadecan-3-ol (AOD) is commonly found in foods contaminated with Fusarium avenaceum, particularly cereals or fruits, and is structurally related to Fusarium mycotoxins (fumonisins) and mammalian sphingoid bases, especially 1-deoxysphinganine (m18:0); therefore, it might enter systemic circulation and tissues upon dietary intake. Knowledge about what happens when cells are exposed to AOD is limited, but it has been reported to be cytotoxic and to induce vacuolization in HepG2 cells. We also found that AOD is cytotoxic for HepG2 cells, but even at a concentration where cell viability remained above 85% (5 μM), it altered 24 differentially expressed genes based on RNA sequencing-based transcriptomic profiling. Among these genes, 13 were shared with cells treated with m18:0. These overlapping differentially expressed genes were primarily enriched in activated stress response pathways of cells, including the upregulation of specific genes in the hypoxia-inducible factor 1α (HIF-1α) signaling pathway, such as hexokinase 1 (HK1) and egl-9 family hypoxia-inducible factor 3 (EGLN3), the activation of key components in the p53 signaling pathway, and the induction of cellular senescence-associated transcriptional programs involving serpin family E member 1 (SERPINE1). Transcriptional analysis of genes related to sphingolipid metabolism showed that treatment with AOD increased the mRNA expression of ceramide synthase 4 (CerS4), sphingosine-1-phosphate phosphatase 1 (SGPP1), and UDP-glucosylceramide glucosyltransferase (UGCG), while decreasing the expression of dihydroceramide desaturase 1 (DEGS1) and fatty acid desaturase 3 (FADS3), a pattern of gene expression changes that mirrored the alterations observed with m18:0 treatment. Lipidomic analyses revealed that AOD significantly perturbed the sphingolipid composition of HepG2 cells, specifically increasing hexosylceramide content while decreasing ceramide and sphingomyelin levels. Moreover, AOD was found to undergo intracellular metabolism to N-acyl-AODs, perhaps by ceramide synthase(s), since this acylation was inhibited by fumonisin B1 (FB1). These findings demonstrate that AOD or possibly its N-acyl metabolites can alter cellular sphingolipid metabolism and affect the expression of genes involved in cell stress. These new insights call for more studies of the impact of this food contaminant on cells and the implications for human health. Full article
(This article belongs to the Special Issue Molecular Response of Hosts to Fungal Toxins)
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17 pages, 2027 KB  
Article
Molecular Variation and Phylogeny within Fusarium avenaceum and Related Species
by Tapani Yli-Mattila, Asmaa Abbas, Olga Gavrilova and Tatiana Gagkaeva
Diversity 2022, 14(7), 574; https://doi.org/10.3390/d14070574 - 18 Jul 2022
Cited by 6 | Viewed by 3846
Abstract
Many recent articles feature research on the Fusarium tricinctum species complex (FTSC), and their authors present different ideas on how the isolates of this species complex can be identified at the species level. In previous studies, our aim was to investigate the phylogeny [...] Read more.
Many recent articles feature research on the Fusarium tricinctum species complex (FTSC), and their authors present different ideas on how the isolates of this species complex can be identified at the species level. In previous studies, our aim was to investigate the phylogeny of FTSC strains, which researchers have morphologically identified as Fusarium avenaceum, Fusarium arthrosporioides, and Fusarium anguioides. In the current study, our phylogenetic maximum parsimony and likelihood analyses of the DNA sequences of the translation elongation factor 1-alpha (TEF1) and combined sequences of TEF1 and beta-tubulin (TUB2) supported the existence of at least four main groups among these strains. Main Group I mainly contains F. avenaceum strains, while Main Group II contains two subgroups, one of which primarily includes F. arthrosporioides strains, and the other mainly includes European F. anguioides strains. Main Group III contains strains from different plants that originated from Asia, including two F. anguioides strains. F. avenaceum strains, which are mostly isolated from different trees, form Main Group IV. A fifth group (Main Group V) was only supported by TEF1 sequences. The main groups previously found by us based on TUB2 sequences could be connected to the new species of the FTSC, which were identified based on TEF1 sequences. In addition, we found strains that significantly differ from Main Groups I-V, and we grouped some of them as single, intermediate, or sister groups. All of the main groups of the present work, and some single and intermediate strains, may represent different species of the FTSC, while the two subgroups of Main Group II constitute intraspecific variation. Regardless of whether they belonged to the main groups, all the analysed strains were able to form different enniatins and 2-amino-14,16-dimethyloctadecan-3-ol, but did not produce beauvericin. Full article
(This article belongs to the Special Issue Diversity of Microbial Eukaryotes)
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16 pages, 463 KB  
Article
Faces of a Changing Climate: Semi-Quantitative Multi-Mycotoxin Analysis of Grain Grown in Exceptional Climatic Conditions in Norway
by Silvio Uhlig, Gunnar Sundstøl Eriksen, Ingerd Skow Hofgaard, Rudolf Krska, Eduardo Beltrán and Michael Sulyok
Toxins 2013, 5(10), 1682-1697; https://doi.org/10.3390/toxins5101682 - 27 Sep 2013
Cited by 125 | Viewed by 10436
Abstract
Recent climatological research predicts a significantly wetter climate in Southern Norway as a result of global warming. Thus, the country has already experienced unusually wet summer seasons in the last three years (2010–2012). The aim of this pilot study was to apply an [...] Read more.
Recent climatological research predicts a significantly wetter climate in Southern Norway as a result of global warming. Thus, the country has already experienced unusually wet summer seasons in the last three years (2010–2012). The aim of this pilot study was to apply an existing multi-analyte LC-MS/MS method for the semi-quantitative determination of 320 fungal and bacterial metabolites in Norwegian cereal grain samples from the 2011 growing season. Such knowledge could provide important information for future survey and research programmes in Norway. The method includes all regulated and well-known mycotoxins such as aflatoxins, trichothecenes, ochratoxin A, fumonisins and zearalenone. In addition, a wide range of less studied compounds are included in the method, e.g., Alternaria toxins, ergot alkaloids and other metabolites produced by fungal species within Fusarium, Penicillium and Aspergillus. Altogether, 46 metabolites, all of fungal origin, were detected in the 76 barley, oats and wheat samples. The analyses confirmed the high prevalence and relatively high concentrations of type-A and -B trichothecenes (e.g., deoxynivalenol up to 7230 µg/kg, HT-2 toxin up to 333 µg/kg). Zearalenone was also among the major mycotoxins detected (maximum concentration 1670 µg/kg). Notably, several other Fusarium metabolites such as culmorin, 2-amino-14,16-dimethyloctadecan-3-ol and avenacein Y were co-occurring. Furthermore, the most prevalent Alternaria toxin was alternariol with a maximum concentration of 449 µg/kg. A number of Penicillium and Aspergillus metabolites were also detected in the samples, e.g., sterigmatocystin in concentrations up to 20 µg/kg. Full article
(This article belongs to the Special Issue Advances in Toxin Detection)
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9 pages, 874 KB  
Communication
Influence of Carbohydrates on Secondary Metabolism in Fusarium avenaceum
by Jens Laurids Sørensen and Henriette Giese
Toxins 2013, 5(9), 1655-1663; https://doi.org/10.3390/toxins5091655 - 24 Sep 2013
Cited by 31 | Viewed by 8031
Abstract
Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in [...] Read more.
Fusarium avenaceum is a widespread pathogen of important crops in the temperate climate zones that can produce many bioactive secondary metabolites, including moniliformin, fusarin C, antibiotic Y, 2-amino-14,16-dimethyloctadecan-3-ol (2-AOD-3-ol), chlamydosporol, aurofusarin and enniatins. Here, we examine the production of these secondary metabolites in response to cultivation on different carbon sources in order to gain insight into the regulation and production of secondary metabolites in F. avenaceum. Seven monosaccharides (arabinose, xylose, fructose, sorbose, galactose, mannose, glucose), five disaccharides (cellobiose, lactose, maltose, sucrose and trehalose) and three polysaccharides (dextrin, inulin and xylan) were used as substrates. Three F. avenaceum strains were used in the experiments. These were all able to grow and produce aurofusarin on the tested carbon sources. Moniliformin and enniatins were produced on all carbon types, except on lactose, which suggest a common conserved regulation mechanism. Differences in the strains was observed for production of fusarin C, 2-AOD-3-ol, chlamydosporol and antibiotic Y, which suggests that carbon source plays a role in the regulation of their biosynthesis. Full article
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