Integrated proteomic and metabolomic analysis reveals the NADH-mediated TCA cycle and energy metabolism disorders based on a new model of chronic progressive heart failure

2013 ◽  
Vol 9 (12) ◽  
pp. 3135 ◽  
Author(s):  
Yong Wang ◽  
Chun Li ◽  
Wenjing Chuo ◽  
Zhongyang Liu ◽  
Yulin Ouyang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Tca Cycle ◽  
Metabolomic Analysis ◽  
New Model ◽  
Progressive Heart Failure

scholarly journals INTEGRATED PROTEOMIC AND METABOLOMIC ANALYSIS REVEALS NADH-MEDIATED TCA ENERGY METABOLISM DISORDER IN CHRONIC PROGRESSIVE HEART FAILURE

Heart ◽  
2012 ◽  
Vol 98 (Suppl 2) ◽  
pp. E115.1-E115 ◽  
Author(s):  
Wang Yong ◽  
Li Chun ◽  
Chuo Wenjing ◽  
Liu Zhongyang ◽  
Ouyang Yulin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Metabolomic Analysis ◽  
Metabolism Disorder ◽  
Progressive Heart Failure ◽  
Energy Metabolism Disorder

scholarly journals Metabolomics coupled with integrated approaches reveals the therapeutic effect of higenamine combined with [6] -gingerol on doxorubicin-induced chronic heart failure in rats

2020 ◽  
Author(s):  
Jianxia Wen ◽  
Xiao Ma ◽  
Ming Niu ◽  
Junjie Hao ◽  
Ying Huang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Chronic Heart Failure ◽  
Acid Metabolism ◽  
Tca Cycle ◽  
Arachidonic Acid Metabolism ◽  
Tunel Staining ◽  
Therapeutic Effects ◽  
Biochemical Indicators ◽  
Serum Biochemical

Abstract Background: This study was aimed to investigate the therapeutic effects and potential mechanism of higenamine combined with [6]-gingerol (HG/[6]-GR) against doxorubicin (DOX) - induced chronic heart failure (CHF) in rats.Materials and methods: Therapeutic effects of HG/[6]-GR on hemodynamics indices, serum biochemical indicators, histopathology and TUNEL staining of rats were assessed. Moreover, a UHPLC-Q-TOF/MS-based serum metabolic approach was performed to identify the metabolites and possible pathways of HG/[6]-GR on DOX-induced CHF. Results: HG/[6]-GR had effects on promoting of hemodynamic indices, alleviating serum biochemical indicators, improving the pathological characteristics of heart tissue and reducing the apoptosis of myocardial cells. Serum metabolisms analyses indicated that the therapeutic effects of HG and [6]-GR were mainly associated with the regulation of eight metabolites, including acetylphosphate, 3-Carboxy-1-hydroxypropylthiamine diphosphate, coenzyme A, palmitic acid, PE(O-18:1(1Z)/20:4(5Z,8Z,11Z,14Z)), oleic acid, lysoPC(18:1(9Z)), and PC(16:0/16:0). Pathway analysis showed that the treatment of HG/[6]-GR on CHF treatment was related to twelve pathways, including glycerophospholipid metabolism, fatty acid metabolism, pantothenate and CoA biosynthesis, citrate cycle (TCA cycle), pyruvate metabolism, and arachidonic acid metabolism. Serum metabolites and metabolic pathways regulated by HG/[6]-GR appear to be related to energy metabolism.Conclusion: Multivariate statistical analysis has provided new insights for understanding CHF and investigating the therapeutic effects and mechanisms of HG/[6]-GR, which influencing the metabolites and pathways related to energy metabolism pathway.

scholarly journals Metabolomics coupled with integrated approaches reveal the therapeutic effects of higenamine combined with [6]-gingerol on doxorubicin-induced chronic heart failure in rats

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Jianxia Wen ◽  
Xiao Ma ◽  
Ming Niu ◽  
Junjie Hao ◽  
Ying Huang ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Chronic Heart Failure ◽  
Acid Metabolism ◽  
Tca Cycle ◽  
Arachidonic Acid Metabolism ◽  
Tunel Staining ◽  
Therapeutic Effects ◽  
Biochemical Indicators ◽  
Serum Biochemical

Abstract Background This study was aimed to investigate the therapeutic effects and potential mechanism of higenamine combined with [6]-gingerol (HG/[6]-GR) against doxorubicin (DOX)—induced chronic heart failure (CHF) in rats. Materials and methods Therapeutic effects of HG/[6]-GR on hemodynamics indices, serum biochemical indicators, histopathology and TUNEL staining of rats were assessed. Moreover, a UHPLC-Q-TOF/MS-based serum metabolic approach was performed to identify the metabolites and possible pathways of HG/[6]-GR on DOX-induced CHF. Results HG/[6]-GR had effects on regulating hemodynamic indices, alleviating serum biochemical indicators, improving the pathological characteristics of heart tissue and reducing the apoptosis of myocardial cells. Serum metabolisms analyses indicated that the therapeutic effects of HG and [6]-GR were mainly associated with the regulation of eight metabolites, including acetylphosphate, 3-Carboxy-1-hydroxypropylthiamine diphosphate, coenzyme A, palmitic acid, PE(O-18:1(1Z)/20:4(5Z,8Z,11Z,14Z)), oleic acid, lysoPC(18:1(9Z)), and PC(16:0/16:0). Pathway analysis showed that HG/[6]-GR on CHF treatment was related to twelve pathways, including glycerophospholipid metabolism, fatty acid metabolism, pantothenate and CoA biosynthesis, citrate cycle (TCA cycle), pyruvate metabolism, and arachidonic acid metabolism. Serum metabolites and metabolic pathways regulated by HG/[6]-GR appear to be related to energy metabolism. Conclusion Multivariate statistical analysis has provided new insights for understanding CHF and investigating the therapeutic effects and mechanisms of HG/[6]-GR, which influencing the metabolites and pathways related to energy metabolism pathway.

Abstract 105: The Novel Heart-specific Ring-finger Protein 207 Regulates Energy Metabolism in Cardiomyocytes

2016 ◽  
Vol 119 (suppl_1) ◽  
Author(s):  
Wataru Mizushima ◽  
Hidehisa Takahashi ◽  
Masashi Watanabe ◽  
Shintarou Kinugawa ◽  
Shouji Matsushima ◽  
...  
Keyword(s):  
Heart Failure ◽  
Energy Metabolism ◽  
Protein Level ◽  
Ring Finger ◽  
Metabolomic Analysis ◽  
Ring Finger Protein ◽  
Finger Protein ◽  
Cardiac Energy Metabolism ◽  
Cardiac Energy ◽  
Ring Finger Proteins

Background: Ring-finger proteins constitute a large protein family in the human genome and play essential roles in various biological processes. However, little is known about heart-specific Ring-finger proteins and those relations with cardiac functions. We performed the comprehensive analysis of the expression profiles of various kinds of Ring-finger proteins and found that Ring-finger protein 207 (RNF207) was largely expressed in the heart. The purpose of our study was to elucidate a role of RNF207 in the heart. Methods and Results: First, we confirmed that RNF207 was predominantly expressed in the heart at the mRNA and protein level. Next, we examined whether the expression of RNF207 changed in transverse aortic constriction (TAC) model mice and coronary ischemic heart failure model mice . 4 weeks after TAC, mRNA level of RNF207 was significantly decreased to approximately 40% of that in sham mice. Moreover, we found that the protein level of RNF207 in the mice with heart failure was significantly reduced to around 70% of that in sham mice. Considering the well-known facts that the heart is a high-energy demanding organ and that the levels of ATP in cardiomyocytes are reduced in those model mice, we hypothesized that RNF207 got involved in cardiac energy metabolism. To investigate the hypothesis, we depleted RNF207 in rat neonatal cardiomyocytes (RNC) and performed metabolomic analysis. Metabolomic analysis revealed that ATP concentration and NADH/NAD + ratio were significantly lower and mitochondrial function was significantly reduced in RNF207 depleted RNC, compared to control NRC. Next, to elucidate the molecular mechanism by which RNF207 had effect on cardiac energy metabolism, we explored RNF207-associated proteins by mass spectrometric analysis. We identified voltage-dependent anion channel 1 (VDAC1) as a RNF207-associated protein. It has been shown that mitochondrial protein VDAC1 plays a crucial role in mitochondrial functions, such as energy metabolism. We confirmed that RNF207 directly interacted with VDAC1 by in vitro binding assay. Our results strongly indicate that RNF207 functions as a regulator of cardiac energy metabolism. Conclusion: RNF207 is a novel heart-specific protein and regulates energy metabolism in cardiomyocytes.

Myocardial Metabolic Imaging in the Clinical Setting

2009 ◽  
Vol 5 (1) ◽  
pp. 15
Author(s):  
Nagara Tamaki ◽  
Yuji Kuge ◽  
Keiichiro Yoshinaga ◽  
◽  
◽  
...  
Keyword(s):  
Heart Failure ◽  
Fatty Acid ◽  
Clinical Setting ◽  
Photon Emission ◽  
Tca Cycle ◽  
Emission Tomography ◽  
Metabolic Imaging ◽  
Myocardial Uptake ◽  
Glucose Utilisation ◽  
Myocardial Metabolic Imaging

Glucose and free fatty acids are a major energy source in the myocardium. Metabolic imaging with single photon emission tomography (SPECT) and positron emission tomography (PET) have been widely used for the evaluation of the pathophysiology of coronary artery disease (CAD) and heart failure. 18F fluorodeoxyglucose (FDG) is a glucose analogue that is used to measure myocardial glucose utilisation. The myocardial uptake of a modified branched fatty acid, 15-(p-[iodine-123] iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP), reflects the activation of fatty-acid metabolism by co-enzyme A (CoA) and indirectly reflects cellular adenosine triphosphate (ATP) production. The turnover rate of the tricarboxylic acid (TCA) cycle reflects the rate of overall myocardial oxidative metabolism. 11C acetate is readily metabolised to CO2 almost exclusively through the TCA cycle. These three major agents have been most commonly used for probing myocardial energy metabolism in vivo. Such metabolic imaging has been used for assessing myocardial viability on the basis of persistent glucose utilisation in ischaemic but viable myocardium. BMIPP and FDG have been identified for locating a recent history of myocardial ischaemia. Furthermore, metabolic imaging is promising for the assessment of the pathophysiology of heart failure and the treatment effect of various drugs, as well as mechanical treatments. In this article we will provide an overview of the application of myocardial metabolic imaging in a clinical setting.

scholarly journals Systemic oxidative stress is associated with lower aerobic capacity and impaired skeletal muscle energy metabolism in heart failure patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takashi Yokota ◽  
Shintaro Kinugawa ◽  
Kagami Hirabayashi ◽  
Mayumi Yamato ◽  
Shingo Takada ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Skeletal Muscle ◽  
Energy Metabolism ◽  
Aerobic Capacity ◽  
Plantar Flexion ◽  
Exercise Intolerance ◽  
Whole Body ◽  
Resonance Spectroscopy ◽  
Systemic Oxidative Stress

AbstractOxidative stress plays a role in the progression of chronic heart failure (CHF). We investigated whether systemic oxidative stress is linked to exercise intolerance and skeletal muscle abnormalities in patients with CHF. We recruited 30 males: 17 CHF patients, 13 healthy controls. All participants underwent blood testing, cardiopulmonary exercise testing, and magnetic resonance spectroscopy (MRS). The serum thiobarbituric acid reactive substances (TBARS; lipid peroxides) were significantly higher (5.1 ± 1.1 vs. 3.4 ± 0.7 μmol/L, p < 0.01) and the serum activities of superoxide dismutase (SOD), an antioxidant, were significantly lower (9.2 ± 7.1 vs. 29.4 ± 9.7 units/L, p < 0.01) in the CHF cohort versus the controls. The oxygen uptake (VO2) at both peak exercise and anaerobic threshold was significantly depressed in the CHF patients; the parameters of aerobic capacity were inversely correlated with serum TBARS and positively correlated with serum SOD activity. The phosphocreatine loss during plantar-flexion exercise and intramyocellular lipid content in the participants' leg muscle measured by 31phosphorus- and 1proton-MRS, respectively, were significantly elevated in the CHF patients, indicating abnormal intramuscular energy metabolism. Notably, the skeletal muscle abnormalities were related to the enhanced systemic oxidative stress. Our analyses revealed that systemic oxidative stress is related to lowered whole-body aerobic capacity and skeletal muscle dysfunction in CHF patients.

scholarly journals Butyrate Prevents TGF-β1-Induced Alveolar Myofibroblast Differentiation and Modulates Energy Metabolism

Metabolites ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 258
Author(s):  
Hyo Yeong Lee ◽  
Somi Nam ◽  
Mi Jeong Kim ◽  
Su Jung Kim ◽  
Sung Hoon Back ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Mitochondrial Dynamics ◽  
Tca Cycle ◽  
Lung Fibroblasts ◽  
Myofibroblast Differentiation ◽  
Pulmonary Fibroblasts ◽  
Matrix Deposition ◽  
Tgf Β1

Idiopathic pulmonary fibrosis (IPF) is a serious lung disease characterized by excessive collagen matrix deposition and extracellular remodeling. Signaling pathways mediated by fibrotic cytokine transforming growth factor β1 (TGF-β1) make important contributions to pulmonary fibrosis, but it remains unclear how TGF-β1 alters metabolism and modulates the activation and differentiation of pulmonary fibroblasts. We found that TGF-β1 lowers NADH and NADH/NAD levels, possibly due to changes in the TCA cycle, resulting in reductions in the ATP level and oxidative phosphorylation in pulmonary fibroblasts. In addition, we showed that butyrate (C4), a short chain fatty acid (SCFA), exhibits potent antifibrotic activity by inhibiting expression of fibrosis markers. Butyrate treatment inhibited mitochondrial elongation in TGF-β1-treated lung fibroblasts and increased the mitochondrial membrane potential (MMP). Consistent with the mitochondrial observations, butyrate significantly increased ADP, ATP, NADH, and NADH/NAD levels in TGF-β1-treated pulmonary fibroblasts. Collectively, our findings indicate that TGF-β1 induces changes in mitochondrial dynamics and energy metabolism during myofibroblast differentiation, and that these changes can be modulated by butyrate, which enhances mitochondrial function.

scholarly journals Metabolomic Analysis to Elucidate Mechanisms of Sunitinib Resistance in Renal Cell Carcinoma

Metabolites ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 1
Author(s):  
Tomonori Sato ◽  
Yoshihide Kawasaki ◽  
Masamitsu Maekawa ◽  
Shinya Takasaki ◽  
Kento Morozumi ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Energy Metabolism ◽  
Cell Carcinoma ◽  
Cell Line ◽  
Cell Lines ◽  
Cancer Progression ◽  
Renal Cell ◽  
Treatment Resistance ◽  
Tca Cycle ◽  
Glutamine Uptake

Metabolomics analysis possibly identifies new therapeutic targets in treatment resistance by measuring changes in metabolites accompanying cancer progression. We previously conducted a global metabolomics (G-Met) study of renal cell carcinoma (RCC) and identified metabolites that may be involved in sunitinib resistance in RCC. Here, we aimed to elucidate possible mechanisms of sunitinib resistance in RCC through intracellular metabolites. We established sunitinib-resistant and control RCC cell lines from tumor tissues of RCC cell (786-O)-injected mice. We also quantified characteristic metabolites identified in our G-Met study to compare intracellular metabolism between the two cell lines using liquid chromatography-mass spectrometry. The established sunitinib-resistant RCC cell line demonstrated significantly desuppressed protein kinase B (Akt) and mesenchymal-to-epithelial transition (MET) phosphorylation compared with the control RCC cell line under sunitinib exposure. Among identified metabolites, glutamine, glutamic acid, and α-KG (involved in glutamine uptake into the tricarboxylic acid (TCA) cycle for energy metabolism); fructose 6-phosphate, D-sedoheptulose 7-phosphate, and glucose 1-phosphate (involved in increased glycolysis and its intermediate metabolites); and glutathione and myoinositol (antioxidant effects) were significantly increased in the sunitinib-resistant RCC cell line. Particularly, glutamine transporter (SLC1A5) expression was significantly increased in sunitinib-resistant RCC cells compared with control cells. In this study, we demonstrated energy metabolism with glutamine uptake and glycolysis upregulation, as well as antioxidant activity, was also associated with sunitinib resistance in RCC cells.

Sign in / Sign up

Export Citation Format

Share Document