Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ.

Merrill, Alfred H.; Echten, G van; Wang, E; Sandhoff, Konrad

doi:10.1016/s0021-9258(19)74249-5

Cited by 334 publications

(43 citation statements)

References 54 publications

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“…Increased dietary fumonisin B1 was suggested to alter the normal digestive and nutrient absorptive functions of the epithetlial lining of the gastrointestinal tract of birds. Further studies have reported the adverse influences of dietary fumonisin on normal epithelial morphology [ 40 ]. Ochratoxin A was reported to induce a similar deleterious effect on intestinal barrier function, indicating a role of mycotoxins in non-specific gastrointestinal tract hypo function in animals [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Mgbeahuruike

Ejiofor

Ashang

et al. 2021

Toxins

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Synergistic interaction of adsorbents in reducing the adverse impacts of mycotoxin on performance and proximate composition of broiler feeds was investigated. Fungal growth was induced by sprinkling water on the feed. S. cerevisiae + bentonite, kaolin + bentonite or S. cerevisiea + kaolin adsorbent combinations (1.5 g/kg feed) were added and the feeds were stored in black polythene bags. An untreated group was kept as a positive control while fresh uncontaminated feed was used as a negative control. Mycotoxins were extracted from the feeds and quantified using reverse phase HPLC. Proximate composition, nutrient digestibility of the feeds, feed intake and weight gain of the broilers were measured. Deoxynivalenol (DON) concentration in the contaminated/untreated feed was 347 µg/kg while aflatoxin B1 (AFB1) was 34 µg/kg. Addition of bentonite and kaolin in the contaminated feed reduced AFB1 and DON to significantly lower levels. Feed intake and weight gain were low in the broilers fed the contaminated feed. The carbohydrate level was significantly (p < 0.05) reduced from 62.31 to 40.10%, crude protein digestibility dropped from 80.67 to 49.03% in the fresh feed and contaminated feed respectively. Addition of the adsorbents (S. cerevisiae and bentonite) significantly (p < 0.05) improved these parameters.

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Section: Discussionmentioning

confidence: 99%

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Mgbeahuruike

Ejiofor

Ashang

et al. 2021

Toxins

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“…Exogenous short chain C 6 -ceramide has been shown to incorporate into cells undergo the recycling of its backbone sphingosine for forming sphingosine-1-phosphate or ceramide by the catalytic action of sphingosine kinase or ceramide synthase, respectively. 13 In our previous studies using SKOV3 cells, C 6 -ceramide blocked the formation of lamellipodia, and inhibition of C 6 -ceramide recycling by fumonisin B1 (a ceramide synthase inhibitor) 28 partially restored the formation of lamellipodia. 16 To assess the impact of exogenous ceramide recycling on the formation of lamellipodia, fumonisin B1 was employed to suppress the recycling of sphingosine backbone for forming ceramide.…”

Section: Roles Of Ceramide Species In the Formation Of Lamellipodiamentioning

confidence: 93%

Ceramide synthase 2‐C _24:1 ‐ceramide axis limits the metastatic potential of ovarian cancer cells

Zhang

Sakamoto²,

Canals³

et al. 2021

FASEB j.

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Regulation of sphingolipid metabolism plays a role in cellular homeostasis, and dysregulation of these pathways is involved in cancer progression. Previously, our reports identified ceramide as an anti-metastatic lipid. In the present study, we investigated the biochemical alterations in ceramide-centered metabolism of sphingolipids that were associated with metastatic potential. We established metastasis-prone sublines of SKOV3 ovarian cancer cells using an in vivo selection method. These cells showed decreases in ceramide levels and ceramide synthase (CerS) 2 expression. Moreover, CerS2 downregulation in ovarian cancer cells promoted metastasis in vivo and potentiated cell motility and invasiveness. Moreover, CerS2 knock-in suppressed the formation of lamellipodia required for cell motility in this cell line. In order to define specific roles of ceramide species in cell motility controlled by CerS2, the effect of exogenous long-and very long-chain ceramide species on the formation of lamellipodia was evaluated. Treatment with distinct ceramides increased cellular ceramides and had inhibitory effects on the formation of lamellipodia. Interestingly, blocking the recycling pathway of ceramides by a CerS inhibitor was ineffective in the suppression of exogenous C 24:1 -ceramide for the formation of lamellipodia. These results suggested that C 24:1 -ceramide, a CerS2 metabolite, predominantly suppresses the formation of lamellipodia without the requirement for deacylation/reacylation. Moreover, knockdown of neutral ceramidase suppressed the formation of lamellipodia concomitant with upregulation of C 24:1 -ceramide. Collectively, the CerS2-C 24:1ceramide axis, which may be countered by neutral ceramidase, is suggested to limit cell motility and metastatic potential. These findings may provide insights that lead to further development of ceramide-based therapy and biomarkers for metastatic ovarian cancer.

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“…To further test whether intact lipid rafts are required for S-PrP-initiated cell-signaling, we pretreated PC12 cells with fumonisin B1 (FM, 25 mM) for 24 h. FM blocks synthesis of sphingolipids that are key components of lipid rafts (34). Fig.…”

Section: Activation Of Cell-signaling By S-prp Requires Lrp1 and Lipid Raftsmentioning

confidence: 99%

A soluble derivative of PrPC activates cell-signaling and regulates cell physiology through LRP1 and the NMDA receptor

Mantuano

Azmoon

Banki

et al. 2020

Journal of Biological Chemistry

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Cellular prion protein (PrPC) is a widely expressed, glycosyl-phosphatidylinositol‑anchored membrane protein. PrPSc is a misfolded and aggregated form of PrPC responsible for prion-induced neurodegenerative diseases. Understanding the function of the nonpathogenic PrPC monomer is an important objective. PrPC may be shed from the cell surface to generate soluble derivatives. Herein, we studied a recombinant derivative of PrPC (S-PrP), which corresponds closely in sequence to a soluble form of PrPC shed from the cell surface by ADAM family proteases. S-PrP activated cell-signaling in PC12 and N2a cells. TrkA was transactivated by Src family kinases (SFKs) and ERK1/2 was activated downstream of Trk receptors. These cell-signaling events were dependent on the N‑methyl-D-aspartate Receptor (NMDA‑R) and Low Density Lipoprotein Receptor‑related Protein‑1 (LRP1), which functioned as a cell-signaling receptor system in lipid rafts. Membrane-anchored PrPC and NCAM were not required for S-PrP-initiated cell-signaling. S‑PrP promoted PC12 cell neurite outgrowth. This response required the NMDA-R, LRP1, SFKs, and Trk receptors. In Schwann cells, S-PrP interacted with the LRP1/NMDA-R receptor system to activate ERK1/2 and promote cell migration. The effects of S-PrP on PC12 cell neurite outgrowth and SC migration were similar to those caused by other proteins that engage the LRP1/NMDA‑R receptor system, including activated α2-macroglobulin and tissue-type plasminogen activator. Collectively, these results demonstrate that shed forms of PrPC may exhibit important biological activities in the CNS and the PNS by serving as ligands for the LRP1/NMDA-R receptor system.

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Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ.

Cited by 334 publications

References 54 publications

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Ceramide synthase 2‐C _24:1 ‐ceramide axis limits the metastatic potential of ovarian cancer cells

A soluble derivative of PrPC activates cell-signaling and regulates cell physiology through LRP1 and the NMDA receptor

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Fumonisin B1 inhibits sphingosine (sphinganine) N-acyltransferase and de novo sphingolipid biosynthesis in cultured neurons in situ.

Cited by 334 publications

References 54 publications

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Reduction of the Adverse Impacts of Fungal Mycotoxin on Proximate Composition of Feed and Growth Performance in Broilers by Combined Adsorbents

Ceramide synthase 2‐C 24:1 ‐ceramide axis limits the metastatic potential of ovarian cancer cells

A soluble derivative of PrPC activates cell-signaling and regulates cell physiology through LRP1 and the NMDA receptor

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Ceramide synthase 2‐C _24:1 ‐ceramide axis limits the metastatic potential of ovarian cancer cells