Inhibition by the fungicide fenpropimorph of cholesterol biosynthesis in 3T3 fibroblasts

Corio-Costet, M F; Gerst, Nicolas; Benveniste, Pierre; Schuber, Francis

doi:10.1042/bj2560829

Cited by 14 publications

(11 citation statements)

References 22 publications

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“…FEN has been shown to inhibit squalene epoxidase in Nectria haematococca var. cucurbitae (Ziogas et al ., ), and to block demethylation of lanosterol during cholesterol synthesis in 3T3 fibroblasts (Corio‐Costet et al ., ). Treatment of 5‐day‐old seedlings with 50–100 μ m FEN for 2–3 h resulted in highly reproducible ABCB19‐GFP puncta (Figure e), and long‐term treatment (for 2.5 days) showed large aggregations (Figure S6).…”

Section: Resultsmentioning

confidence: 97%

Sterols and sphingolipids differentially function in trafficking of the Arabidopsis ABCB19 auxin transporter

et al. 2013

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SUMMARYThe Arabidopsis ATP-binding cassette B19 (ABCB19, P-glycoprotein19) transporter functions coordinately with ABCB1 and PIN1 to motivate long-distance transport of the phytohormone auxin from the shoot to root apex. ABCB19 exhibits a predominantly apolar plasma membrane (PM) localization and stabilizes PIN1 when the two proteins co-occur. Biochemical evidence associates ABCB19 and PIN1 with sterol-and sphingolipid-enriched PM fractions. Mutants deficient in structural sterols and sphingolipids exhibit similarity to abcb19 mutants. Sphingolipid-defective tsc10a mutants and, to a lesser extent, sterol-deficient cvp1 mutants phenocopy abcb19 mutants. Live imaging studies show that sterols function in trafficking of ABCB19 from the trans-Golgi network to the PM. Pharmacological or genetic sphingolipid depletion has an even greater impact on ABCB19 PM targeting and interferes with ABCB19 trafficking from the Golgi. Our results also show that sphingolipids function in trafficking associated with compartments marked by the VTI12 syntaxin, and that ABCB19 mediates PIN1 stability in sphingolipid-containing membranes. The TWD1/FKBP42 co-chaperone immunophilin is required for exit of ABCB19 from the ER, but ABCB19 interactions with sterols, sphingolipids and PIN1 are spatially distinct from FKBP42 activity at the ER. The accessibility of this system to direct live imaging and biochemical analysis makes it ideal for the modeling and analysis of sterol and sphingolipid regulation of ABCB/P-glycoprotein transporters.

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Section: Resultsmentioning

confidence: 97%

Sterols and sphingolipids differentially function in trafficking of the Arabidopsis ABCB19 auxin transporter

et al. 2013

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“…Fenpropimorph is not exclusively toxic to fungi. It also affects plants (Raederstorff & Rohmer 1987a; Grove, Fair & Moss 1996), bacteria (Hesselink, Kerkenaar & Witholt 1990) and mammalian cells (Corio‐Costet et al . 1988).…”

Section: Discussionmentioning

confidence: 99%

The impact of the fungicide fenpropimorph (Corbel®) on bacterivorous and fungivorous protozoa in soil

Ekelund

1999

Journal of Applied Ecology

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Summary 0[ The ability of indigenous soil protozoa to survive and multiply when exposed to various concentrations of the fungicide fenpropimorph was investigated[ The number of protozoan taxa in relation to biocide concentration was examined in enrichment cultures[ The population dynamics of bacterivorous and fungivorous protozoa\ hyphal forming units\ and respiration activity were followed in soil microcosms amended with glucose and various concentrations of fenpropimorph[ 1[ The average number of~agellate taxa detected in 49!mg portions of air!dried soil declined from 01 to zero with fenpropimorph concentrations increasing from 9 to 59 mg L Ð0 [ Naked amoebae and ciliates were present at all fenpropimorph concen! trations[ The 49!mg soil portions initially contained 0=8 × 09 2 heterotrophic~agel! lates\ 0=3 × 09 2 naked amoebae and about 4 ciliates[ The presence of the two latter groups even at concentrations of 59 mg L Ð0 therefore suggests that they are more tolerant to fenpropimorph than the soil~agellates[ 2[ The addition of glucose had a strong stimulatory e}ect on soil respiration\ which lasted for about 19 days[ Soil respiration in microcosms amended with glucose and pesticide was of the same order as in systems with glucose only^however\ soil res! piration was signi_cantly impeded in microcosm systems with a low pesticide content and stimulated in systems with a high pesticide content[ 3[ Bacterivorous protozoa "naked amoebae and heterotrophic~agellates# were a}ec! ted at all tested concentrations "9=63Ð649 mg L Ð0 # of fenpropimorph[ High con! centrations\ 5=5Ð649 mg L Ð0

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“…It is worth noting that fenpropimorph itself was recently described as a sigma ligand exerting long term neuroprotective properties in glutamate neurotoxicity models (25). On the other hand, fenpropimorph was found to inhibit cholesterol biosynthesis in 3T3 cells (28), its main target appearing to be lanosterol demethylase. This inhibitory effect on an upstream enzyme might expectedly have masked the one on SI that we have clearly observed using recombinant yeast strains devoid of endogenous SI (see Fig.…”

Section: Expression Of the Murine Cdna Restores Aerobic Viability Andmentioning

confidence: 99%

Emopamil-binding Protein, a Mammalian Protein That Binds a Series of Structurally Diverse Neuroprotective Agents, Exhibits Δ8-Δ7 Sterol Isomerase Activity in Yeast

Silve

Dupuy

Labit-Lebouteiller

et al. 1996

Journal of Biological Chemistry

123

104

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Delta8-delta7 sterol isomerase is an essential enzyme on the sterol biosynthesis pathway in eukaryotes. This endoplasmic reticulum-resident membrane protein catalyzes the conversion of delta8-sterols to their corresponding delta7-isomers. No sequence data for high eukaryote sterol isomerase being available so far, we have cloned a murine sterol isomerase-encoding cDNA by functional complementation of the corresponding deficiency in the yeast Saccharomyces cerevisiae. The amino acid sequence deduced from the cDNA open reading frame is highly similar to human emopamil-binding protein (EBP), a protein of unknown function that constitutes a molecular target for neuroprotective drugs. A yeast strain in which the sterol isomerase coding sequence has been replaced by that of human EBP or its murine homologue recovers the ability to convert delta8-sterol into delta7-sterol, both in vivo and in vitro. In these recombinant strains, both cell proliferation and the sterol isomerization reaction are inhibited by the high affinity EBP ligand trifluoperazine, as is the case in mammalian cells but not in wild type yeast cell. In contrast, the recombinant strains are much less susceptible to the sterol inhibition effect of haloperidol and fenpropimorph, as compared with wild type yeast strains. Our results strongly suggest that EBP and delta8-delta7 sterol isomerase are identical proteins in mammals.

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Inhibition by the fungicide fenpropimorph of cholesterol biosynthesis in 3T3 fibroblasts

Cited by 14 publications

References 22 publications

Sterols and sphingolipids differentially function in trafficking of the Arabidopsis ABCB19 auxin transporter

Sterols and sphingolipids differentially function in trafficking of the Arabidopsis ABCB19 auxin transporter

The impact of the fungicide fenpropimorph (Corbel®) on bacterivorous and fungivorous protozoa in soil

Emopamil-binding Protein, a Mammalian Protein That Binds a Series of Structurally Diverse Neuroprotective Agents, Exhibits Δ8-Δ7 Sterol Isomerase Activity in Yeast

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