Integrated Metabolomics-DNA Methylation Analysis Reveals Significant Long-Term Tissue-Dependent Directional Alterations in Aminoacyl-tRNA Biosynthesis in the Left Ventricle of the Heart and Hippocampus Following Proton Irradiation

被引：17

作者：

Torres, Eileen Ruth S. ^{[1
]}

Hall, Reed ^{[1
]}

Bobe, Gerd ^{[2
,3
]}

Choi, Jaewoo ^{[2
,4
]}

Impey, Soren ^{[5
,6
]}

Pelz, Carl ^{[5
,6
]}

Lindner, Jonathan R. ^{[7
,8
]}

Stevens, Jan F. ^{[2
,4
]}

Raber, Jacob ^{[1
,4
,8
,9
,10
]}

机构：

[1] Oregon Hlth & Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA

[2] Oregon Hlth & Sci Univ, Linus Pauling Inst, Portland, OR 97201 USA

[3] Oregon State Univ, Dept Anim & Rangeland Sci, Corvallis, OR 97331 USA

[4] Oregon State Univ, Coll Pharm, Dept Pharmaceut Sci, Corvallis, OR 97331 USA

[5] Oregon Hlth & Sci Univ, Oregon Stem Cell Ctr, Portland, OR 97201 USA

[6] Oregon Hlth & Sci Univ, Dept Pediat, 3181 Sw Sam Jackson Pk Rd, Portland, OR 97201 USA

[7] Oregon Hlth & Sci Univ, Oregon Natl Primate Res Ctr, Portland, OR 97201 USA

[8] Oregon Hlth & Sci Univ, Knight Cardiovasc Inst, Portland, OR 97201 USA

[9] Oregon Hlth & Sci Univ, Div Neurosci ONPRC, Dept Neurol, Portland, OR 97201 USA

[10] Oregon Hlth & Sci Univ, Div Neurosci ONPRC, Dept Radiat Med, Portland, OR 97201 USA

来源：

FRONTIERS IN MOLECULAR BIOSCIENCES | 2019年 / 6卷

基金：

美国国家卫生研究院;

关键词：

proton irradiation; hippocampus; left ventricle; integrated epigenetic metabolomics analysis; radiation biomarkers; Parkinson's disease; RADIATION; NEURONS; RADIOTHERAPY; CONNECTIONS; PARTICLES; EXPOSURE; THERAPY; QUALITY; MODELS; LIFE;

D O I：

10.3389/fmolb.2019.00077

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

In this study, an untargeted metabolomics approach was used to assess the effects of proton irradiation (1 Gy of 150 MeV) on the metabolome and DNA methylation pattern in the murine hippocampus and left ventricle of the heart 22 weeks following exposure using an integrated metabolomics-DNA methylation analysis. The integrated metabolomics-DNA methylation analysis in both tissues revealed significant alterations in aminoacyl-tRNA biosynthesis, but the direction of change was tissue-dependent. Individual and total amino acid synthesis were downregulated in the left ventricle of proton-irradiated mice but were upregulated in the hippocampus of proton-irradiated mice. Amino acid tRNA synthetase methylation was mostly downregulated in the hippocampus of proton-irradiated mice, whereas no consistent methylation pattern was observed for amino acid tRNA synthetases in the left ventricle of proton-irradiated mice. Thus, proton irradiation causes long-term changes in the left ventricle and hippocampus in part through methylation-based epigenetic modifications. Integrated analysis of metabolomics and DNA methylation is a powerful approach to obtain converging evidence of pathways significantly affected. This in turn might identify biomarkers of the radiation response, help identify therapeutic targets, and assess the efficacy of mitigators directed at those targets to minimize, or even prevent detrimental long-term effects of proton irradiation on the heart and the brain.

引用

页数：9