Novel fluorescent ceramide derivatives for probing ceramidase substrate specificity

Bhabak, Krishna P.; Proksch, Denny; Redmer, Susanne; Arenz, Christoph

doi:10.1016/j.bmc.2012.08.035

Cited by 27 publications

(15 citation statements)

References 55 publications

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“…Fluorescence spectroscopy-based methods to determine ceramidase activity have gained attention due to their high sensitivities and signal-to-noise ratios. In this context, different fl uorophores, such as NBD ( 21-23 ), BODIPY, ( 24 ), lissamine-rhodamine ( 24 ), and Nile Red ( 25 ) have been incorporated into either the fatty acyl or the sphingoid base moiety to produce fl uorescent (dihydro)ceramides as ceramidase substrates. Despite the advantage of fl uorescent over radioactive methods, the former are not amenable for high-throughput formats.…”

Section: Discussionmentioning

confidence: 99%

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Casasampere

Camacho

Cingolani

et al. 2015

Journal of Lipid Research

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Section: Discussionmentioning

confidence: 99%

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Casasampere

Camacho

Cingolani

et al. 2015

Journal of Lipid Research

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“…Acid ceramidase physically interacts with SF-1 and co-localizes to the nucleus in living cells (Lucki et al, 2012). Since lipids of the phospholipid-class chemically lack the N-acyl bond ceramidases hydrolyze (Fig 2E) (Bhabak et al, 2012), ceramidases cannot act on phospholipids such as PIP2, PIP3 or PC. Phospholipids may therefore decouple SF-1 from direct sphingolipid signaling pathways (Lucki et al, 2012; Urs et al, 2006), enabling the SF-1 circuit to operate independently of that branch of the full network.…”

Section: Phospholipids Can Chemically Decouple Sf-1 From Particular Smentioning

confidence: 99%

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

Blind

2014

Advances in Biological Regulation

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An unresolved problem in biological signal transduction is how particular branches of highly interconnected signaling networks can be decoupled, allowing activation of specific circuits within complex signaling architectures. Although signaling dynamics and spatiotemporal mechanisms serve critical roles, it remains unclear if these are the only ways cells achieve specificity within networks. The transcription factor Steroidogenic Factor-1 (SF-1) is an excellent model to address this question, as it forms dynamic complexes with several chemically distinct lipid species (phosphatidylinositols, phosphatidylcholines and sphingolipids). This property is important since lipids bound to SF-1 are modified by lipid signaling enzymes (IPMK & PTEN), regulating SF-1 biological activity in gene expression. Thus, a particular SF-1/lipid complex can interface with a lipid signaling enzyme only if SF-1 has been loaded with a chemically compatible lipid substrate. This mechanism permits dynamic downstream responsiveness to constant upstream input, disentangling specific pathways from the full network. The potential of this paradigm to apply generally to nuclear lipid signaling is discussed, with particular attention given to the nuclear receptor superfamily of transcription factors and their phospholipid ligands.

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“…[16] Towards this end, CERT was expressed and purified from E. coli cells as described previously. [2b] Briefly, an NBD derivative of ceramide [17] was pulled down together with the His-tagged CERT using Ni-NTA magnetic beads, and the bound fraction was quantified afterwards by its fluorescence intensity. Addition of the respective competitors reduced the amount of NBD-Cer-C 16 pulled down together with CERT ( Table 1).…”

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confidence: 99%

Facile Synthesis of the CERT Inhibitor HPA‐12 and Some Novel Derivatives

Saied

Diederich

2014

Chemistry An Asian Journal

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HPA-12 is an inhibitor of CERT-mediated non-vesicular transport of ceramide from the ER membranes to the Golgi apparatus. The inhibitor effectively blocks the synthesis of the membrane lipid sphingomyelin and may represent a novel drug prototype. Previous syntheses relied on non-commercial catalysts or specialized chemistries. Here we present a straightforward and effective method to synthesize HPA-12 from commercially available protected L-serinol in four steps. Some new analogues were synthesized and evaluated for their CERT-binding activity.

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Novel fluorescent ceramide derivatives for probing ceramidase substrate specificity

Cited by 27 publications

References 55 publications

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Activity of neutral and alkaline ceramidases on fluorogenic N-acylated coumarin-containing aminodiols

Disentangling biological signaling networks by dynamic coupling of signaling lipids to modifying enzymes

Facile Synthesis of the CERT Inhibitor HPA‐12 and Some Novel Derivatives

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