Sedoheptulose-1,7-bisphospate Accumulation and Metabolic Anomalies in Hepatoma Cells Exposed to Oxidative Stress

Cheng, Mei‐Ling; Lin, Jui-Fen; Huang, Cheng-Yu; Li, Guan-Jie; Shih, Lu-Min; Chiu, Daniel T.; Ho, Hung‐Yao

doi:10.1155/2019/5913635

Cited by 10 publications

(9 citation statements)

References 54 publications

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“…The NAD+ depletion and NADH accumulation on the cellwide dimension was accompanied by a metabolic balance shift to oxidative phosphorylation (oxphos) over glycolysis. This study along with the other similar findings discussed that the oxphos inhibition leads to parthanatos due to rapid PARP-dependent ATP deprivation demonstrating that oxphos is a vital factor for recovery and survival of the damaged cell (34,35,65).…”

Section: Discussionsupporting

confidence: 76%

“…Zhang et al reported that PAPR1 inhibitors can counteract the NAD+ depletion caused by atrial fibrillation and alleviate oxidative stress and DNA damage in cardiomyocytes (57). Other studies have demonstrated that PARP1 inhibitors can improve the survival rate of HepG2 cells under oxidative stress, and metabolomics analysis technology has confirmed that its protective effect is related to NAD+ depletion caused by excessive activation of PARP1 (35). However, so far there is no report on the use of PARP1 inhibitors to protect SCNs under ozone exposure conditions.…”

Section: Discussionmentioning

confidence: 99%

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Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons

Zhao

Zhang

et al. 2020

Front. Med.

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Background and Objective: Ozone therapy has shown therapeutic efficacy in different disorders particularly low back pain (LBP). However, ozone therapy has been associated with toxic effects on the respiratory, endocrine, cardiovascular systems as well as nervous system because of its strong oxidizing capacity. Recent studies have reported possible associations between ozone exposure and metabolic disorders, but the findings are controversial and little is known on the mechanisms of action. This study aims to investigate the cytotoxic effects of ozone exposure and possible mechanism of action in the animal model.Methods: Wistar neonate rats with the age of 24 h after birth were sacrificed by cervical dislocation under general anesthesia, then immersed in 75% alcohol and iodophor for 5 min, respectively. The spinal cord was isolated and cut to samples of ~1 mm3 and prepared for further experiments. The spinal cord neurons (SCNs) were exposed to ozone at different concentrations and then cultured in 96-well plates with glass bottom for 7 days. The cell viability, ATP levels and the NAD+ concentration were determined and compared between the different experimental groups and the control group.Results: Analyses of the data by non-targeted liquid chromatography-mass spectrometry (LC-MS) analysis determined the metabolic disorder in SCNs following the ozone exposure. Moreover, our assessments showed that ozone exposure resulted in DNA damage, poly (ADP)-ribose polymerase-1 (PARP1) excessive activation, nicotinamide adenine dinucleotide (NAD+) depletion and decrease of ATP level in SCNs. The PARP1 inhibitor can inhibit the cytotoxic effect of ozone to SCNs without inhibiting the activation of AMP-activated protein kinase (AMPK). Our findings revealed that the cytotoxic effects of ozone to SCNs might be mediated by excessive PARP1 activation and subsequent NAD+ depletion. Moreover, using PARP1 inhibitor can protect SCNs from cytotoxic effects of ozone by preventing NAD+ depletion during ozone exposure.Conclusion: Ozone exposure seems to induce metabolic disorders and NAD+ depletion through excessive PARP1 activation in SCNs.

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Section: Discussionsupporting

confidence: 76%

Section: Discussionmentioning

confidence: 99%

Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons

Zhao

Zhang

et al. 2020

Front. Med.

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“…The pentose phosphate pathway (PPP), paralleling an approximate 11-fold increase in sedoheptulose 1/7 phosphate, was altered in WB-affected tissues. Previous studies showed that hydrogen peroxide treatments elevated sedoheptulose 1/7 phosphate levels in hepatoma HepG2 cells ( 58 ). Because the PPP activation was reported to be involved in cyto-protection against oxidative damage ( 59 ), our data suggested that oxidative stress might increase the flux of glucose into the PPP pathway.…”

Section: Discussionmentioning

confidence: 96%

Muscle Metabolome Profiles in Woody Breast-(un)Affected Broilers: Effects of Quantum Blue Phytase-Enriched Diet

et al. 2020

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Woody breast (WB) myopathy is significantly impacting modern broilers and is imposing a huge economic burden on the poultry industry worldwide. Yet, its etiology is not fully defined. In a previous study, we have shown that hypoxia and the activation of its upstream mediators (AKT/PI3K/mTOR) played a key role in WB myopathy, and supplementation of quantum blue (QB) can help to reduce WB severity via modulation of hypoxia-related pathways. To gain further insights, we undertook here a metabolomics approach to identify key metabolite signatures and outline their most enriched biological functions. Ultra performance liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS) identified a total of 108 known metabolites. Of these, mean intensity differences at P < 0.05 were found in 60 metabolites with 42 higher and 18 lower in WB-affected compared to unaffected muscles. Multivariate analysis and Partial Least Squares Discriminant analysis (PLS-DA) scores plot displayed different clusters when comparing metabolites profile from affected and unaffected tissues and from moderate (MOD) and severe (SEV) WB muscles indicating that unique metabolite profiles are present for the WB-affected and unaffected muscles. To gain biologically related molecule networks, a stringent pathway analyses was conducted using IPA knowledge-base. The top 10 canonical pathways generated, using a fold-change −1.5 and 1.5 cutoff, with the 50 differentially abundant-metabolites were purine nucleotide degradation and de novo biosynthesis, sirtuin signaling pathway, citrulline-nitric oxide cycle, salvage pathways of pyrimidine DNA, IL-1 signaling, iNOS, Angiogenesis, PI3K/AKT signaling, and oxidative phosphorylation. The top altered bio-functions in term of molecular and cellular functions in WB-affected tissues included cellular development, cellular growth and proliferation, cellular death and survival, small molecular biochemistry, inflammatory response, free radical scavenging, cell signaling and cell-to-cell interaction, cell cycles, and lipid, carbohydrate, amino acid, and nucleic acid metabolisms. The top disorder functions identified were organismal injury and abnormalities, cancer, skeletal and muscular disorders, connective tissue disorders, and inflammatory diseases. Greene et al. Quantum Blue and Metabolome in Broilers Breast tissues from birds fed with high dose (2,000 FTU) of QB phytase exhibited 22 metabolites with significantly different levels compared to the control group with a clear cluster using PLS-DA analysis. Of these 22 metabolites, 9 were differentially abundant between WB-affected and unaffected muscles. Taken together, this study determined many metabolic signatures and disordered pathways, which could be regarded as new routes for discovering potential mechanisms of WB myopathy.

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“…Liquid chromatography-time-of-flight-mass spectrometry (LC-TOF-MS) was performed, as previously described [36]. Liquid chromatographic separation was performed on an ACQUITY 1.8 µm HSST3 C18 column (100 mm × 2.1 mm) (Waters Corp., Milford, MA, USA) using an ACQUITY Ultra Performance Liquid Chromatography (UPLC) system (Waters Corp., Milford, MA, USA).…”

Section: Metabolomic Analysismentioning

confidence: 99%

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

Cheng

Chien

Lai

et al. 2020

Cells

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Enterovirus 71 (EV71) infection is an endemic disease in Southeast Asia and China. We have previously shown that EV71 virus causes functional changes in mitochondria. It is speculative whether EV71 virus alters the host cell metabolism to its own benefit. Using a metabolomics approach, we demonstrate that EV71-infected Vero cells had significant changes in metabolism. Glutathione and its related metabolites, and several amino acids, such as glutamate and aspartate, changed significantly with the infectious dose of virus. Other pathways, including glycolysis and tricarboxylic acid cycle, were also altered. A change in glutamine/glutamate metabolism is critical to the viral infection. The presence of glutamine in culture medium was associated with an increase in viral replication. Dimethyl α-ketoglutarate treatment partially mimicked the effect of glutamine supplementation. In addition, the immunoblot analysis revealed that the expression of glutamate dehydrogenase (GDH) and trifunctional carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD) increased during infection. Knockdown of expression of glutaminase (GLS), GDH and CAD drastically reduced the cytopathic effect (CPE) and viral replication. Furthermore, we found that CAD bound VP1 to promote the de novo pyrimidine synthesis. Our findings suggest that virus may induce metabolic reprogramming of host cells to promote its replication through interactions between viral and host cell proteins.

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Sedoheptulose-1,7-bisphospate Accumulation and Metabolic Anomalies in Hepatoma Cells Exposed to Oxidative Stress

Cited by 10 publications

References 54 publications

Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons

Ozone Exposure Induces Metabolic Disorders and NAD+ Depletion Through PARP1 Activation in Spinal Cord Neurons

Muscle Metabolome Profiles in Woody Breast-(un)Affected Broilers: Effects of Quantum Blue Phytase-Enriched Diet

Metabolic Reprogramming of Host Cells in Response to Enteroviral Infection

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