Metabolomic approaches to polyamines including acetylated derivatives in lung tissue of mice with asthma
Recently, the relationship between polyamine (PA) metabolism and asthma has been studied in severe asthmatic therapy, but systematic PA metabolism including their acetylated derivatives was not fully understood.
Profiling analysis of polyamines (PAs) was performed to understand the biochemical events and monitor altered PA metabolism in lung tissue of mice with asthma.
Polyamine profiling of lung tissue of mice with asthma was performed without derivatization by liquid chromatography–tandem mass spectrometry (LC–MS/MS) combined with star pattern recognition analysis. The PA levels between control and asthma groups were evaluated by multivariate analysis.
In mouse lung tissue, seven PAs were determined by LC–MS/MS in multiple reaction monitoring (MRM) mode. Their levels were normalized to the corresponding mean levels of the control group for star pattern analysis, which showed distorted heptagonal shapes with characteristic and readily distinguishable patterns for each group. Levels of putrescine (p < 0.0034), N1-acetylputrescine (p < 0.0652), and N8-acetylspermidine (p < 0.0827) were significantly increased in asthmatic lung tissue. The separation of the two groups was evaluated using multivariate analysis. In unsupervised learning, acetylated PAs including N1-acetylspermine were the main metabolites for discrimination. In supervised learning, putrescine and N1-acetylputrescine were evaluated as important metabolites.
The present results provide basic data for understanding polyamine metabolism in asthma and may help to improve the therapy for severe asthma patients.
KeywordsMetabolomics Polyamine profiling analysis Acetylated polyamines Asthma Lung tissue Star pattern recognition analysis Liquid chromatography–tandem mass spectrometry
This work was supported by a National Research Foundation of Korea (NRF) Grant funded by the Ministry of Science, ICT & Future Planning (2015R1A4A1041219), the Ministryof Education, Science, and Technology (2015R1D1A3A01016103) and by the Suncheon Research Center for Natural Medicines.
H-SL performed method development, optimization and validation including application to asthma mice. Y-HH performed sampling of asthma model. CS, MJ and JM performed optimization of method. HJP, YK, THS and SC performed pre-analytical experiments and sample preparation. AKP performed interpretation of statistical analysis. HK, S-TY and GL performed interpretation of the results. M-JP designed the experiments and supervised this work. All of authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving animals were in accordance with the ethical standards of the Institutional Animal Care and Use Committee in the Sunchon National University.
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