title: Aberrant purine metabolism in allergic asthma revealed by plasma metabolomics.
abstract: Asthma is a disease characterized by chronic relapsing airways, and its etiology remains incompletely understood. To better understand the metabolic phenotypes of asthma, we investigated a plasma metabolic signature associated with allergic asthma in ovalbumin (OVA)-sensitized mice by using ultra high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Sixteen metabolites were characterized as potential pathological biomarkers related to asthma. Among them, 6 (dodecanoic acid (P1), myristic acid (P2), phytosphingosine (P3), sphinganine (P4), inosine (P13) and taurocholic acid (P15)) were first reported to have potential relevance in the pathogenesis of experimental asthma. The identified potential biomarkers were involved in 6 metabolic pathways and achieved the most entire metabolome contributing to the formation of allergic asthma. Purine metabolism was the most prominently influenced in OVA-induced asthma mice according to the metabolic pathway analysis (MetPA), suggesting that significantly changes in inflammatory responses in the pathophysiologic process of asthma. The metabolites of purine metabolism, especially uric acid (P12) and inosine (P13), may denote their potential as targeted biomarkers related to experimental asthma. The decreased plasma uric acid (P12) suggested that inflammation responses of allergic asthma inhibited the activity of xanthine oxidase in purine metabolism, and manifested the severity of asthma exacerbation. The increased level of inosine (P13) suggests that inflammatory cells induce adenosine triphosphate (ATP) breakdown, resulting in excessive expression of adenosine deaminase (ADA) in the formation of allergic asthma. These findings provided a novel perspective on the metabolites signatures related to allergic asthma, which provided us with new insights into the pathogenesis of asthma, and the discovery of targets for clinical diagnosis and treatment.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Meng
authors.initials: M
authors.lastname: Yu
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Feng-Xia
authors.initials: FX
authors.lastname: Cui
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Jia
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhou
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Hong-Wu
authors.initials: HW
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China.
authors.forename: Gang
authors.initials: G
authors.lastname: Ding
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, PR China. Electronic address: zmzou@implad.ac.cn.
authors.forename: Zhong-Mei
authors.initials: ZM
authors.lastname: Zou
mesh_terms: D000818:Animals; D001249:Asthma / Q000097:blood* / Q000139:chemically induced; D005260:Female; D006967:Hypersensitivity / Q000097:blood*; D055432:Metabolomics / Q000379:methods*; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000633:toxicity; D010949:Plasma / Q000378:metabolism; D011687:Purines / Q000378:metabolism*
chemical_list: D011687:Purines; D010047:Ovalbumin
keywords: Allergic asthma; Inosine; Plasma metabolomics; Purine metabolism; UPLC-Q-TOF/MS; Uric acid