Effect of L-Cycloserine on Cellular Responses Mediated by Macrophages and T Cells

Cho, Jae Youl

doi:10.1248/bpb.30.2105

Cited by 4 publications

(2 citation statements)

References 60 publications

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“…1), LCS has been piloted in several seizure models, including petit-mal seizures in the rat (Marescaux et al 1985) and audiogenic seizures in mice (Polc et al 1986). Nonetheless, clinical development of LCS has been hampered because it also inhibits the first enzyme of sphingolipid formation, 3-ketodihydrosphingosine synthase (serine palmitoyltransferase; Cho 2007). The capacity of LCS to elevated intracerebral GABA is dose-dependent, with smaller doses (10–30 mg/kg p.o.…”

Section: Treatment Strategies For Ssadh Deficiencymentioning

confidence: 99%

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Vogel

Pearl

Theodore

et al. 2012

J of Inher Metab Disea

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Summary This review summarizes a presentation made at the retirement Symposium of Prof. dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L-cycloserine, the GHB receptor antagonist NCS-382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open-label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742.

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Section: Treatment Strategies For Ssadh Deficiencymentioning

confidence: 99%

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Vogel

Pearl

Theodore

et al. 2012

J of Inher Metab Disea

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show abstract

“…glucosylceramide (GlcCer)) (9) and more complex glycosphingolipids (10–12). Likewise, macrophage behavior can be modified by inhibition of de novo sphingolipid biosynthesis by l -cycloserine (13) and myriocin (14) and by sphingolipid analogs such as FTY720 (15), PCERA-1 (Cer-1-P analog) (16), and α-galactosylceramide (α-GalCer) (17), among others.…”

Section: Introductionmentioning

confidence: 99%

Kdo2-Lipid A, a TLR4-specific Agonist, Induces de Novo Sphingolipid Biosynthesis in RAW264.7 Macrophages, Which Is Essential for Induction of Autophagy

Sims

Haynes

Kelly

et al. 2010

Journal of Biological Chemistry

107

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Activation of RAW264.7 cells with a lipopolysaccharide specific for the TLR4 receptor, Kdo2-lipid A (KLA), causes a large increase in cellular sphingolipids, from 1.5 to 2.6 × 109 molecules per cell in 24 h, based on the sum of subspecies analyzed by “lipidomic” mass spectrometry. Thus, this study asked the following question. What is the cause of this increase and is there a cell function connected with it? The sphingolipids arise primarily from de novo biosynthesis based on [U-13C]palmitate labeling, inhibition by ISP1 (myriocin), and an apparent induction of many steps of the pathway (according to the distribution of metabolites and microarray analysis), with the exception of ceramide, which is also produced from pre-existing sources. Nonetheless, the activated RAW264.7 cells have a higher number of sphingolipids per cell because KLA inhibits cell division; thus, the cells are larger and contain increased numbers of membrane vacuoles termed autophagosomes, which were detected by the protein marker GFP-LC3. Indeed, de novo biosynthesis of sphingolipids performs an essential structural and/or signaling function in autophagy because autophagosome formation was eliminated by ISP1 in KLA-stimulated RAW264.7 cells (and mutation of serine palmitoyltransferase in CHO-LYB cells); furthermore, an anti-ceramide antibody co-localizes with autophagosomes in activated RAW264.7 cells versus the Golgi in unstimulated or ISP1-inhibited cells. These findings establish that KLA induces profound changes in sphingolipid metabolism and content in this macrophage-like cell line, apparently to produce sphingolipids that are necessary for formation of autophagosomes, which are thought to play important roles in the mechanisms of innate immunity.

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Activation of PPARα by bezafibrate negatively affects de novo synthesis of sphingolipids in regenerating rat liver

Zabielski

Baranowski

Żendzian-Piotrowska

et al. 2010

Prostaglandins & Other Lipid Mediators

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Effect of L-Cycloserine on Cellular Responses Mediated by Macrophages and T Cells

Cited by 4 publications

References 60 publications

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

Kdo2-Lipid A, a TLR4-specific Agonist, Induces de Novo Sphingolipid Biosynthesis in RAW264.7 Macrophages, Which Is Essential for Induction of Autophagy

Activation of PPARα by bezafibrate negatively affects de novo synthesis of sphingolipids in regenerating rat liver

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