TY  - JOUR
A1  - Reichel, Martin
A1  - Hoenig, Stefanie
A1  - Liebisch, Gerhard
A1  - Lüth, Anja
A1  - Kleuser, Burkhard
A1  - Gulbins, Erich
A1  - Schmitz, Gerd
A1  - Kornhuber, Johannes
T1  - Alterations of plasma glycerophospholipid and sphingolipid species in male alcohol-dependent patients
JF  - Biochimica et biophysica acta : Molecular and cell biology of lipids
N2  - Background: Alcohol abuse is a major risk factor for somatic and neuropsychiatric diseases. Despite their potential clinical importance, little is known about the alterations of plasma glycerophospholipid (GPL) and sphingolipid (SPL) species associated with alcohol abuse.
 Methods: Plasma GPL and SPL species were quantified using electrospray ionization tandem mass spectrometry in samples from 23 male alcohol-dependent patients before and after detoxification, as well as from 20 healthy male controls.
 Results: A comparison of alcohol-dependent patients with controls revealed higher phosphatidylcholine (PC; P-value = 0.008) and phosphatidylinositol (PI; P-value = 0.001) concentrations in patients before detoxification, and higher PI (P-value = 0.001) and phosphatidylethanolamine (PE)-based plasmalogen (PEP; P-value = 0.003) concentrations after detoxification. Lysophosphatidylcholines (LPC) were increased by acute intoxication (P-value = 0.002). Sphingomyelin (SM) concentration increased during detoxification (P-value = 0.011). The concentration of SM 23:0 was lower in patients (P-value = 2.79 x 10(-5)), and the concentrations of ceramide Cer d18:1/16:0 and Cer d18:1/18:0 were higher in patients (P-value = 2.45 x 10(-5) and 3.73 x 10(-5)). Activity of lysosomal acid sphingomyelinase (ASM) in patients correlated positively with the concentrations of eight LPC species, while activity of secreted ASM was inversely correlated with several PE, PI and PC species, and positively correlated with the molar ratio of PC to SM (Pearson's r = 0.432; P-value = 0.039).
 Conclusion: Plasma concentrations of numerous GPL and SPL species were altered in alcohol-dependent patients. These molecules might serve as potential biomarkers to improve the diagnosis of patients and to indicate health risks associated with alcohol abuse. Our study further indicates that there are strong interactions between plasma GPL concentrations and SPL metabolism. (C) 2015 Elsevier B.V. All rights reserved.
KW  - Acid sphingomyelinase
KW  - Alcohol dependence
KW  - Anxiety
KW  - Cardiovascular
KW  - Case-control study
KW  - Ceramide
KW  - Clinical
KW  - Depression
KW  - Diagnostic
KW  - Disease
KW  - Glycerophospholipids
KW  - Lysophosphatidylcholines
KW  - Mass spectrometry
KW  - Phosphatidylcholines
KW  - Phosphatidylinositols
KW  - Plasma
KW  - Plasmalogens
KW  - Sphingolipids
KW  - Sphingomyelin
KW  - Tandem mass spectrometry
Y1  - 2015
U6  - https://doi.org/10.1016/j.bbalip.2015.08.005
SN  - 1388-1981
SN  - 0006-3002
VL  - 1851
IS  - 11
SP  - 1501
EP  - 1510
PB  - Elsevier
CY  - Amsterdam
ER  - 
TY  - JOUR
A1  - Putra, Sulistyo Emantoko Dwi
A1  - Neuber, Corinna
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
A1  - Kleuser, Burkhard
T1  - Analysis of genomic DNA methylation levels in human placenta using liquid Chromatography-Electrospray ionization tandem mass spectrometry
JF  - Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry and pharmacology
N2  - Background: DNA-methylation is a common epigenetic tool which plays a crucial role in gene regulation and is essential for cell differentiation and embryonic development. The placenta is an important organ where gene activity can be regulated by epigenetic DNA modifications, including DNA methylation. This is of interest as, the placenta is the interface between the fetus and its environment, the mother. Exposure to environmental toxins and nutrition during pregnancy may alter DNA methylation of the placenta and subsequently placental function and as a result the phenotype of the offspring. The aim of this study was to develop a reliable method to quantify DNA methylation in large clinical studies. This will be a tool to analyze the degree of DNA methylation in the human placenta in relationship to clinical readouts. Methods: Liquid chromatography-electrospray ionization/multi-stage mass spectrometry (LC-ESI/MS/MS) technique was used for the quantification of the 5dmC/dG ratio in placentas from 248 healthy pregnancies. We were able to demonstrate that this method is a reliable and stable way to determine global placental DNA methylation in large clinical trials. Results/Conclusion: The degree of placental DNA methylation seen in our pilot study varies substantially from 2% to 5%. The clinical implications of this variation need to be demonstrated in adequately powered large studies.
KW  - Pregnancy
KW  - Placenta
KW  - Methylation
KW  - Global
KW  - LC-MS/MS
KW  - Fetal programming
KW  - Clinical
Y1  - 2014
U6  - https://doi.org/10.1159/000358666
SN  - 1015-8987
SN  - 1421-9778
VL  - 33
IS  - 4
SP  - 945
EP  - 952
PB  - Karger
CY  - Basel
ER  -