Ammonium Ion Exchanged Zeolite for Laser Desorption/Ionization Mass Spectrometry of Phosphorylated Peptides

Yang, Mujie; Fujino, Tatsuya

doi:10.1155/2015/513761

Cited by 1 publication

(1 citation statement)

References 15 publications

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“…For example, unesterified cholesterol, commonly detected at 386 m/z or 369 m/z (M + H -H2O) using this method (Schiller, Zschornig et al 2001) was detected in MALDI-TOF MS but was not confirmed using MALDI-TOF MS/MS. It is possible that the matrix used (2,5-DHB) for analysis had too many matrix-related low mass peaks corresponding to it, making identification of unesterified cholesterol problematic (Yang and Fujino 2015). An additional limitation is the quantification of lipids using MALDI-TOF MS. Quantification can be difficult as crystallisation of the analyte and matrix does not form a uniform layer over the target surface, therefore signals from the analyte may be variable (Duncan, Roder et al 2008).…”

Section: Lipid Analysismentioning

confidence: 99%

Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model

Hammond¹

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<p>Niemann-Pick type C (NPC) disease is a rare neuro-visceral, lysosomal storage disorder for which no effective therapy yet exists. A recessive mutation in the late endosomal/lysosomal cholesterol transport genes NPC1 (95%) or NPC2 (5%) are the causative factors which leads to an accumulation of unesterified cholesterol and sphingolipids in the late endosome/lysosome. It is a build-up of these lipids that, in the majority of cases, ultimately leads to premature death prior to adolescence. In recent years, an imbalance of histone acetylation in a yeast model of NPC disease and subsequently an increased expression of histone deacetylase genes in NPC patient fibroblasts relative to healthy controls was discovered. This led to the finding that Vorinostat (suberoylanilide hydroxamic acid (SAHA); Zolinza®) a histone deacetylase inhibitor (HDACi) drug, rescued unesterified cholesterol accumulation in NPC patient fibroblasts. From these findings in NPC patient fibroblasts, a Phase I clinical trial testing the efficacy of orally-administered Vorinostat in adult NPC disease patients commenced in 2014; however, the therapeutic efficacy of Vorinostat in a whole animal model of NPC disease has not been investigated and is thus unknown. In this thesis, the therapeutic efficacy of intra-peritoneal administered 150 mg/kg Vorinostat in the Npc1nmf164 mouse was explored. This internationally approved HDACi reduced liver disease by decreasing lipid accumulation without increasing expression of NPC1; however, the treatment did not delay weight loss, onset of ataxia and premature death, possibly due to insufficient concentrations penetrating through the blood brain barrier. Transcriptome analysis suggested Vorinostat improved liver disease in a pleiotropic manner, not surprising given the epigenetic nature of HDACi at the gene expression level. Overall, the results herein are of particular importance to the current clinical trial where the therapeutic efficacy is being investigated without any knowledge of efficacy in an animal of NPC disease.</p>

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Section: Lipid Analysismentioning

confidence: 99%

Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model

Hammond¹

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show abstract

Ammonium Ion Exchanged Zeolite for Laser Desorption/Ionization Mass Spectrometry of Phosphorylated Peptides

Cited by 1 publication

References 15 publications

Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model

Vorinostat, a Histone Deacetylase Inhibitor, as a Candidate Therapy to Treat Liver Pathology in a Niemann-Pick type C Disease Mouse Model

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