Purine Metabolism in Heart Failure: Oxidant Biology and Therapeutic Indications

Bauer, John; Moffatt-Bruce, Susan D.; Elton, Terry S.; Feldman, David N.

doi:10.1111/j.1751-7133.2008.00011.x

Cited by 8 publications

(7 citation statements)

References 6 publications

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“…45 It has been considered that xanthine oxidase could generate excess oxygen-free radicals and increasingly release of inosine (8), then caused ischemia injury in the pathway. 46 Significantly, increase of inosine (8) was observed in present study, which has been reported as a marker of ischemic myocardium in urinary metabonomic study. 18 The decreased xanthosine (20) detected by NMR was also involved in purine metabolism, which was an important process in myocardial ischemia injury.…”

Section: Molecular Biosystems Papersupporting

confidence: 63%

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics

et al. 2013

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Myocardial infarction (MI) is a leading cause of morbidity and mortality but the precise mechanism of its pathogenesis remains obscure. To achieve the most comprehensive screening of the entire metabolome related to isoproterenol (ISO) induced-MI, we present a tissue targeted metabonomic study using an integrated approach of ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF MS) and proton nuclear magnetic resonance (1H NMR). Twenty-two metabolites were detected as potential biomarkers related to the formation of MI, and the levels of pantothenic acid (), lysoPC(18:0) (), PC(18:4(6Z,9Z,12Z,15Z)/18:0) (), taurine (), lysoPC(20:3(8Z,11Z,14Z)) (), threonine (), alanine (), creatine (), phosphocreatine (), glucose 1-phosphate (), glycine (), xanthosine (), creatinine () and glucose () were decreased significantly, while the concentrations of histamine (), L-palmitoylcarnitine (), GSSG (), inosine (), arachidonic acid (), linoelaidic acid (), 3-methylhistamine () and glycylproline () were increased significantly in the MI rats compared with the control group. The identified potential biomarkers were involved in twelve metabolic pathways and achieved the most entire metabolome contributing to the injury of the myocardial tissue. Five pathways, including taurine and hypotaurine metabolism, glycolysis, arachidonic acid metabolism, glycine, serine and threonine metabolism and histidine metabolism, were significantly influenced by ISO-treatment according to MetPA analysis and suggested that the most prominent changes included inflammation, interference of calcium dynamics, as well as alterations of energy metabolism in the pathophysiologic process of MI. These findings provided a unique perspective on localized metabolic information of ISO induced-MI, which gave us new insights into the pathogenesis of MI, discovery of targets for clinical diagnosis and treatment.

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Section: Molecular Biosystems Papersupporting

confidence: 63%

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics

et al. 2013

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“…Significantly increase of inosine ( 8 ) was observed in present study, which has been reported as a marker of ischemic myocardium in urinary metabonomic study 37 . The decreased xanthosine ( 20 ) detected by NMR were also involved in purine metabolism, which was an important process in myocardial ischemia injury 38 . The reason for its reduction in myocardium of MI rat is probably related to the degradation of ATP, of which the elevated biosynthesis from biomolecules, such as xanthosine and lead to xanthosine decreasing in MI group.…”

Section: Resultsmentioning

confidence: 99%

Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats

Liu

Zhou

Jia

et al. 2016

Sci Rep

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Xin-Ke-Shu (XKS) is a traditional Chinese patent medicine used for treatment of coronary heart diseases in China. However, its mechanism of action is still unclear. In this paper, the mediation of XKS on the isoproterenol (ISO)-induced myocardial infarction (MI) rat were evaluated based on a tissue-targeted metabonomics in vitro/vivo. The result indicated that twelve metabolic pathways were involved in the therapeutic effect of XKS in vivo, where seven pathways were associated with the Ca2+ overloading mechanism. In agreement with regulation on metabolic variations, XKS markedly reversed the over-expressions of three involved proteins including phospholipase A2 IIA (PLA2 IIA), calcium/calmodulin-dependent protein kinase II (CaMK II) and Pro-Caspase-3. The metabolic regulations of XKS on H9c2 cell also partially confirmed its metabolic effect. These metabolic characteristics in vitro/vivo and western blotting analysis suggested that XKS protected from MI metabolic perturbation major via inhibition of Ca2+ overloading mechanism. Furthermore, 11 active ingredients of XKS exerted steady affinity with the three proteins through the molecular docking study. Our findings indicate that the metabonomics in vitro/vivo combined with western blotting analysis offers the opportunity to gain insight into the comprehensive efficacy of TCMs on the whole metabolic network.

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“…The UHPLC-MS spectra also showed a build-up of cyclic AMP and a decrease of xanthosine. The two metabolites are both involved in purine metabolism, which was an important process in myocardial ischemia injury [47], [48]. Among them, Cyclic AMP is a metabolite of ATP.…”

Section: Discussionmentioning

confidence: 99%

Metabonomic Profiles Delineate the Effect of Traditional Chinese Medicine Sini Decoction on Myocardial Infarction in Rats

et al. 2012

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BackgroundIn spite of great advances in target-oriented Western medicine for treating myocardial infarction (MI), it is still a leading cause of death in a worldwide epidemic. In contrast to Western medicine, Traditional Chinese medicine (TCM) uses a holistic and synergistic approach to restore the balance of Yin-Yang of body energy so the body's normal function can be restored. Sini decoction (SND) is a well-known formula of TCM which has been used to treat MI for many years. However, its holistic activity evaluation and mechanistic understanding are still lacking due to its complex components.Methodology/Principal FindingsA urinary metabonomic method based on nuclear magnetic resonance and ultra high-performance liquid chromatography coupled to mass spectrometry was developed to characterize MI-related metabolic profiles and delineate the effect of SND on MI. With Elastic Net for classification and selection of biomarkers, nineteen potential biomarkers in rat urine were screened out, primarily related to myocardial energy metabolism, including the glycolysis, citrate cycle, amino acid metabolism, purine metabolism and pyrimidine metabolism. With the altered metabolism pathways as possible drug targets, we systematically analyze the therapeutic effect of SND, which demonstrated that SND administration could provide satisfactory effect on MI through partially regulating the perturbed myocardial energy metabolism.Conclusions/SignificanceOur results showed that metabonomic approach offers a useful tool to identify MI-related biomarkers and provides a new methodological cue for systematically dissecting the underlying efficacies and mechanisms of TCM in treating MI.

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Purine Metabolism in Heart Failure: Oxidant Biology and Therapeutic Indications

Cited by 8 publications

References 6 publications

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics

The metabolic disturbances of isoproterenol induced myocardial infarction in rats based on a tissue targeted metabonomics

Standardized Chinese Formula Xin-Ke-Shu inhibits the myocardium Ca2+ overloading and metabolic alternations in isoproterenol-induced myocardial infarction rats

Metabonomic Profiles Delineate the Effect of Traditional Chinese Medicine Sini Decoction on Myocardial Infarction in Rats

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