Fumonisins: fungal toxins that shed light on sphingolipid function

Merrill, Alfred H.; Liotta, Dennis; Riley, Ronald T.

doi:10.1016/0962-8924(96)10021-0

Cited by 137 publications

(109 citation statements)

References 44 publications

Supporting

Mentioning

106

Contrasting

Unclassified

Order By: Relevance

“…Taken together, these results suggest that the fate of exogenous dihydrosphingosine appears to be a result of the distinct action of the DHS-1-P phosphatase and the DHS-1-P/S-1-P lyase with the latter enzyme being responsible for the shift of sphingolipid metabolites into glycerolipids. These data are in agreement with previous studies that have suggested a relationship between sphingolipid and glycerolipid metabolism (1,2). For example, treatment of yeast or mammalian cells with the mycotoxin fumonisin B1, which blocks sphingolipid biosynthesis, resulted in an elevation in the concentrations of free sphingoid bases such as dihydrosphingosine, phytosphingosine, and dihydrosphingosine 1-phosphate as well as an increase in the concentrations of glycerolipids (23,24).…”

Section: Table III Purification and Substrate Specificity Of Flag Fussupporting

confidence: 82%

See 1 more Smart Citation

Identification and Characterization of Saccharomyces cerevisiae Dihydrosphingosine-1-phosphate Phosphatase

Mao

Wadleigh

Jenkins

et al. 1997

Journal of Biological Chemistry

151

131

View full text Add to dashboard Cite

We have identified the yeast sphingosine resistance gene (YSR2) of Saccharomyces cerevisiae as encoding a protein that specifically dephosphorylates dihydrosphingosine 1-phosphate (DHS-1-P), and we refer to this protein as dihydrosphingosine-1-phosphate phosphatase. Overexpression of YSR2 conferred sphingosine resistance to the dihydrosphingosine-1-P lyase-defective mutant (JS16) of S. cerevisiae, which is hypersensitive to sphingosine. The ysr2⌬ deletion mutant of S. cerevisiae accumulated DHS-1-P compared with its wild type strain upon labeling with D-erythro-[4,5-3 H]dihydrosphingosine, whereas overexpression of YSR2 increased dephosphorylation of DHS-1-P. An epitopetagged fusion protein (YSR2-Flag) was partially purified and found to specifically dephosphorylate DHS-1-P to yield dihydrosphingosine. YSR2 failed to dephosphorylate ceramide 1-phosphate or phosphatidic acid. Functionally, the mutant bearing the ysr2⌬ deletion decreased labeling of sphingolipids and increased labeling of glycerolipids dramatically following in vivo labeling with D-erythro-[ 3 H]dihydrosphingosine, but it slightly affected labeling of sphingolipids with inositol. Taken together, these results identify YSR2 as dihydrosphingosine-1-phosphate phosphatase. They also raise the intriguing possibility that phosphorylation followed by dephosphorylation is required for incorporation of exogenous long chain sphingoid bases into sphingolipids.Sphingolipids are important components of eukaryotic cell membranes. Animals develop different diseases due to genetically or environmentally altered sphingolipid metabolism (1, 2). Sphingolipids have structural functions in maintaining cell membrane integrity, and they act as anchors to proteins (3). In addition, metabolites of sphingolipids such as ceramide, sphingosine, and sphingosine 1-phosphate (S-1-P) 1 have been demonstrated to be involved as bioeffector molecules and second messengers in key events including cell growth, differentiation, cell senescence, apoptosis, and stress responses (1-5). S-1-P has a proliferative effect on certain quiescent cells and has been shown to trigger intracellular calcium mobilization (5). Platelet-derived growth factor induces an elevation in cellular levels of sphingosine and S-1-P and activates sphingosine kinase in quiescent fibroblasts. These studies imply that S-1-P participates in the mitogenic action of this and other growth factors (6).In the yeast Saccharomyces cerevisiae, sphingolipids have been demonstrated to be essential for cell viability, based on studies of long chain sphingoid base auxotrophs that are defective in serine palmitoyltransferase, the first enzyme in the de novo pathway of sphingolipid synthesis (7). Importantly, at least some sphingolipid-mediated cell events are conserved between mammalian cells and S. cerevisiae (8). For example, ceramide induces S. cerevisiae growth suppression and cell cycle arrest, and the mammalian counterpart of ceramide-activated protein phosphatase has been identified in S. cerevisiae (9).In this report, we ...

show abstract

Section: Table III Purification and Substrate Specificity Of Flag Fussupporting

confidence: 82%

“…onstrated to be involved as bioeffector molecules and second messengers in key events including cell growth, differentiation, cell senescence, apoptosis, and stress responses (1)(2)(3)(4)(5). S-1-P has a proliferative effect on certain quiescent cells and has been shown to trigger intracellular calcium mobilization (5).…”

mentioning

confidence: 99%

Identification and Characterization of Saccharomyces cerevisiae Dihydrosphingosine-1-phosphate Phosphatase

Mao

Wadleigh

Jenkins

et al. 1997

Journal of Biological Chemistry

151

131

View full text Add to dashboard Cite

show abstract

“…or greater (Nelson et al, 1993;Sydenham et al, 1991). Ingestion of fumonisin through contaminated feed, or as pure FB 1 , has been shown to induce a variety of responses in the challenged animals including neuro-, renal-or hepatoxicosis and neoplasms as well as cell death (Gelderblom et al, ,b, 1992Marasas et al, 1988a;Merrill et al, 1996;Nelson et al, 1993;Tolleson et al, 1996). Because of the frequency and level of contamination of maize and the toxicity of fumonisin to animals, serious concern exists over the dual roles involving proliferation and apoptosis these mycotoxins may play in animal and human disease.…”

Section: Sphinganine Analog Mycotoxins (Sams)mentioning

confidence: 99%

“…The fact that the SAMs bear structural relationships to sphinganine and sphingosine suggested a connection to sphingolipids. Several reports now link the affects of the fumonisins on animals and cultured animal cells to altered sphingolipid metabolism (reviewed by Merrill et al, 1996Merrill et al, , 1997Yoo et al, 1994).…”

Section: Connection Of Ceramide Signaling To Toxicity Of Sams and Apomentioning

confidence: 99%

“…Signal transduction involving ceramide and sphingoid bases has emerged as an important lipid-based second messenger system in development, cell proliferation and degenerative diseases in animals through regulating a diversity of responses from gene expression to kinase cascades (Chao, 1995;Merrill et al, 1996Merrill et al, , 1997Obeid and Hannun, 1995;Pena et al, 1997). The linkage of ceramide signaling to apoptosis, cancer, and degenerative disease in animals is now driving a rapidly emerging novel area in signal transduction in animal biology (Hannun, 1996).…”

Section: Ceramide Signaling and Apoptosis In Animals And Plantsmentioning

confidence: 99%

See 1 more Smart Citation

Mycotoxins reveal connections between plants and animals in apoptosis and ceramide signaling

Gilchrist

1997

Cell Death Differ

View full text Add to dashboard Cite

Plants undergo programmed cell death during development and disease in contexts that are functionally analogous to apoptosis in animals. Recent studies involving plant cell death induced by mycotoxins, pathogens and lethal mutations along with the cell-autonomous death during development now point to several conserved connections to apoptosis in animals. Morphological markers indicative of apoptosis recently reported in plants include TUNEL positive cells, DNA ladders, Ca 2+ -activated nucleosomal DNA cleavage, and formation of apoptotic-like bodies that occur in some but not all situations involving ordered cell death. In parallel studies with animal and plant cells treated with sphinganine analog mycotoxins our results indicate that the induction and inhibition of death may be mediated by ceramide-linked signaling systems. The presence and significance of ceramide-linked second messenger systems is well documented in animals but is virtually unknown in plants. Further research will discern the manner in which the important function of programmed cell death is conserved as well as diverged between the two kingdoms.

show abstract

Structure determination of soybean and wheat glucosylceramides by tandem mass spectrometry

et al. 2000

View full text Add to dashboard Cite

Glucosylceramide (GluCer) is a major sphingolipid of plant tissue and, thus, abundant in nature and in dietary food sources. The lipid backbones of mammalian GluCer (sphingosine, d18 : 1Δ4, and ceramide) induce cell death (apoptosis) and inhibit colon carcinogenesis, it is critical to know the structures of GluCer present in plants as a first step toward understanding this potential link between diet and cancer. This study characterized the molecular species of GluCer from soybean and wheat by low‐resolution, high‐resolution and tandem mass spectrometry. Soybean GluCer was comprised primarily (>95%) of ceramide with 4,8‐sphingadiene (d18 : 2Δ4,Δ8) and α‐hydroxypalmitic acid (h16 : 0); the remainder had the same backbone with h18 : 0, h20 : 0, h22 : 0 and h24 : 0 fatty acids. Wheat GluCer had three major ceramide, d18 : 2Δ4,Δ8 with h16 : 0, d18 : 1Dgr;8 with h16 : 0 and d18 : 2Δ4,Δ8 with h20 : 0, and smaller amounts of other homologs. These backbones differ from those of mammalian sphingolipids, which often have a Δ4‐double bond (but rarely a Δ8‐double bond), and have α‐hydroxy fatty acids in only some cases. Previously unexplained fragmentations that were diagnostic for the type of sphingoid base backbone (i.e. by homolytic cleavage of the doubly allylic C‐6—C‐7 bond to yield a stable distonic allylic radical cation and an allylic radical neutral) were also identified. Hence this method should be useful in the identification of double bonds in sphingolipids, and structure–function relationships between sphingolipids and colon carcinogenesis. Copyright © 2000 John Wiley & Sons, Ltd.

show abstract

Fumonisins: fungal toxins that shed light on sphingolipid function

Cited by 137 publications

References 44 publications

Identification and Characterization of Saccharomyces cerevisiae Dihydrosphingosine-1-phosphate Phosphatase

Identification and Characterization of Saccharomyces cerevisiae Dihydrosphingosine-1-phosphate Phosphatase

Mycotoxins reveal connections between plants and animals in apoptosis and ceramide signaling

Structure determination of soybean and wheat glucosylceramides by tandem mass spectrometry

Contact Info

Product

Resources

About