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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/29786648/utilizing-optimized-tools-to-investigate-ptm-crosstalk-identifying-potential-ptm-crosstalk-of-acetylated-mitochondrial-proteins
#1
Henrick Horita, Andy Law, Kim Middleton
Post-translational modification (PTM) crosstalk is recognized as a major cell-regulatory mechanism, and studies of several proteins have validated the premise that PTMs work in concert. Previous work by our group investigated the potential PTM crosstalk on proteins in the EGFR-Ras-c-Fos axis by utilizing a comprehensive set of PTM reagents termed Signal-Seeker toolkits. In this study, these tools were used to investigate the potential PTM crosstalk that occurs in acetylated mitochondrial proteins in response to a mitochondrial stress-inducing agent hydrogen peroxide (H₂O₂)...
May 22, 2018: Proteomes
https://www.readbyqxmd.com/read/29784770/tlr-activated-repression-of-fe-s-cluster-biogenesis-drives-a-metabolic-shift-and-alters-histone-and-tubulin-acetylation
#2
Wing-Hang Tong, Nunziata Maio, De-Liang Zhang, Erika M Palmieri, Hayden Ollivierre, Manik C Ghosh, Daniel W McVicar, Tracey A Rouault
Given the essential roles of iron-sulfur (Fe-S) cofactors in mediating electron transfer in the mitochondrial respiratory chain and supporting heme biosynthesis, mitochondrial dysfunction is a common feature in a growing list of human Fe-S cluster biogenesis disorders, including Friedreich ataxia and GLRX5-related sideroblastic anemia. Here, our studies showed that restriction of Fe-S cluster biogenesis not only compromised mitochondrial oxidative metabolism but also resulted in decreased overall histone acetylation and increased H3K9me3 levels in the nucleus and increased acetylation of α-tubulin in the cytosol by decreasing the lipoylation of the pyruvate dehydrogenase complex, decreasing levels of succinate dehydrogenase and the histone acetyltransferase ELP3, and increasing levels of the tubulin acetyltransferase MEC17...
May 22, 2018: Blood Advances
https://www.readbyqxmd.com/read/29780561/triple-action-pt-iv-derivatives-of-cisplatin-a-new-class-of-potent-anticancer-agents-that-overcome-resistance
#3
Emanuele Petruzzella, Roman Sirota, Irene Solazzo, Valentina Gandin, Dan Gibson
A series of triple action Pt(iv) prodrugs was designed to test the hypothesis that multi-action compounds, where each bioactive moiety intervenes in several cellular processes, might be more effective than a single agent at killing cancer cells. In particular, "triple action" Pt(iv) derivatives of cisplatin, where the axial ligands are inhibitors of cyclooxygenase (COXi), histone deacetylase (HDACi) or pyruvate dehydrogenase kinase (PDKi) were developed. All compounds, ctc-[Pt(NH3 )2 (COXi)(PDKi)Cl2 ], ctc-[Pt(NH3 )2 (COXi)(HDACi)Cl2 ] and ctc-[Pt(NH3 )2 (HDACi)(PDKi)Cl2 ], where COXi = aspirin or ibuprofen, PDKi = dichloroacetate and HDACi = valproate or phenylbutyrate, were significantly more cytotoxic than cisplatin against all cell lines of an in-house panel of human cancer cells...
May 14, 2018: Chemical Science
https://www.readbyqxmd.com/read/29779823/the-role-of-thiamine-dependent-enzymes-in-obesity-and-obesity-related-chronic-disease-states-a-systematic-review
#4
REVIEW
Donogh Maguire, Dinesh Talwar, Paul G Shiels, Donald McMillan
The WHO 2016 report indicates that worldwide obesity is rising, with over 600 million people in the obese range (BMI>30). The recommended daily calorie intake for adults is 2000 kcal and 2500 kcal for women and men respectively. The average American consumes 3770 kcal/day and the average person in the UK consumes 3400 kcal/day. With such increased caloric intake, there is an increased load on metabolic pathways, in particular glucose metabolism. Such metabolism requires micronutrients as enzyme co-factors...
June 2018: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/29779216/glutamate-metabolism-in-cerebral-mitochondria-after-ischemia-and-post-ischemic-recovery-during-aging-relationships-with-brain-energy-metabolism
#5
Federica Ferrari, Antonella Gorini, Siegfried Hoyer, Roberto Federico Villa
Glutamate is involved in cerebral ischemic injury, but its role has not been completely clarified and studies are required to understand how minimize its detrimental effects, contemporarily boosting the positive ones. In fact, glutamate is not only a neurotransmitter, but primarily a key metabolite for brain bioenergetics. Thus, we investigated the relationships between glutamate and brain energy metabolism in an in vivo model of complete cerebral ischemia of 15 min and during post-ischemic recovery after 1, 24, 48, 72 and 96 hrs in 1 year- adult and 2 year-old aged rats...
May 20, 2018: Journal of Neurochemistry
https://www.readbyqxmd.com/read/29778095/establishing-an-innovative-carbohydrate-metabolic-pathway-for-efficient-production-of-2-keto-l-gulonic-acid-in-ketogulonicigenium-robustum-initiated-by-intronic-promoters
#6
Cai-Yun Wang, Ye Li, Zi-Wei Gao, Li-Cheng Liu, Meng-Yue Zhang, Tian-Yuan Zhang, Chun-Fu Wu, Yi-Xuan Zhang
BACKGROUND: 2-Keto-L-gulonic acid (2-KGA), the precursor of vitamin C, is currently produced by two-step fermentation. In the second step, L-sorbose is transformed into 2-KGA by the symbiosis system composed of Ketogulonicigenium vulgare and Bacillus megaterium. Due to the different nutrient requirements and the uncertain ratio of the two strains, the symbiosis system significantly limits strain improvement and fermentation optimization. RESULTS: In this study, Ketogulonicigenium robustum SPU_B003 was reported for its capability to grow well independently and to produce more 2-KGA than that of K...
May 19, 2018: Microbial Cell Factories
https://www.readbyqxmd.com/read/29777685/thiamine-preserves-mitochondrial-function-in-a-rat-model-of-traumatic-brain-injury-preventing-inactivation-of-the-2-oxoglutarate-dehydrogenase-complex
#7
Garik V Mkrtchyan, Muammer Üçal, Andrea Müllebner, Sergiu Dumitrescu, Martina Kames, Rudolf Moldzio, Marek Molcanyi, Samuel Schaefer, Adelheid Weidinger, Ute Schaefer, Juergen Hescheler, Johanna Catharina Duvigneau, Heinz Redl, Victoria I Bunik, Andrey V Kozlov
BACKGROUND AND PURPOSE: Based on the fact that traumatic brain injury is associated with mitochondrial dysfunction we aimed at localization of mitochondrial defect and attempted to correct it by thiamine. EXPERIMENTAL APPROACH: Interventional controlled experimental animal study was used. Adult male Sprague-Dawley rats were subjected to lateral fluid percussion traumatic brain injury. Thiamine was administered 1 h prior to trauma; cortex was extracted for analysis 4 h and 3 d after trauma...
May 16, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29775761/the-bone-anabolic-effects-of-irisin-are-through-preferential-stimulation-of-aerobic-glycolysis
#8
Dingdong Zhang, ChuHyun Bae, Junghak Lee, Jiho Lee, Zeyu Jin, Myeongmo Kang, Young Suk Cho, Jeong-Han Kim, Weontae Lee, Sung-Kil Lim
Irisin, a recently identified hormone secreted by skeletal muscle in response to exercise, exhibits anabolic effects on the skeleton primarily through the stimulation of bone formation. However, the mechanism underlying the irisin-stimulated anabolic response remains largely unknown. To uncover the underlying mechanism, we biosynthesized recombinant irisin (r-irisin) using an Escherichia coli expression system and used it to treat several osteoblast cell types. Our synthesized r-irisin could promote proliferation and differentiation of osteoblasts as evidenced by enhanced expression of osteoblast-specific transcriptional factors, including Runt-related transcription factor-2 (Runx2), Oster (Osx), as well as early osteoblastic differentiation markers such as alkaline phosphatase (Alp) and collagen type I alpha 1 (Col1a1)...
May 15, 2018: Bone
https://www.readbyqxmd.com/read/29771492/hyperpolarized-13c-mrs-reveals-the-rate-limiting-role-of-the-blood-brain-barrier-on-the-cerebral-uptake-and-metabolism-of-l-lactate-in-vivo
#9
Yuhei Takado, Tian Cheng, Jessica A M Bastiaansen, Hikari Yoshihara, Bernard Lanz, Mor Mishkovsky, Sylvain Lengacher, Arnaud Comment
The dynamics of L-lactate transport across the blood-brain barrier (BBB) and its cerebral metabolism are still subject to debate. We studied lactate uptake and intracellular metabolism in the mouse brain using hyperpolarized 13C magnetic resonance spectroscopy (MRS). Following the intravenous injection of hyperpolarized [1-13C]lactate, we observed that the distribution of 13C label between lactate and pyruvate, which has been shown to be representative of their pool size ratio, is different in NMRI and C57BL/6 mice, the latter exhibiting a higher cerebral lactate dehydrogenase A (Ldha) expression...
May 17, 2018: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/29764469/chibby-suppresses-aerobic-glycolysis-and-proliferation-of-nasopharyngeal-carcinoma-via-the-wnt-%C3%AE-catenin-lin28-let7-pdk1-cascade
#10
Cheng-Fu Cai, Guo-Dong Ye, Dong-Yan Shen, Wei Zhang, Mao-Li Chen, Xin-Xin Chen, Da-Xiong Han, Yan-Jun Mi, Qi-Cong Luo, Wang-Yu Cai, Shu-Yu Yang
BACKGROUND: Great progress has been achieved in the study of the aerobic glycolysis or the so-called Warburg effect in a variety of cancers; however, the regulation of the Warburg effect in Nasopharyngeal carcinoma (NPC) has not been completely defined. METHODS: Gene expression pattern of NPC cells were used to test associations between Chibby and β-catenin expression. Chibby siRNAs and over-expression vector were transfected into NPC cells to down-regulate or up-regulate Chibby expression...
May 15, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29764240/ferrous-glycinate-regulates-cell-energy-metabolism-by-restricting-hypoxia-induced-factor-1%C3%AE-expression-in-human-a549-cells
#11
Yung-Ting Kuo, Jhong-Huei Jheng, Mei-Chen Lo, Wei-Lu Chen, Shyang-Guang Wang, Horng-Mo Lee
Iron or oxygen regulates the stability of hypoxia inducible factor-1α (HIF-1α). We investigated whether ferrous glycinate would affect HIF-1α accumulation, aerobic glycolysis and mitochondrial energy metabolism in human A549 lung cancer cells. Incubation of A549 cells with ferrous glycinate decreased the protein levels of HIF-1α, which was abrogated by proteosome inhibitor, or prolyl hydroxylase inhibitor. Addition of ferrous glycinate decreased protein levels of glucose transporter-1, hexokinase-2, and lactate dehydrogenase A, and decreased pyruvate dehydrogenase kinase-1 (PDK-1) and pyruvate dehydrogenase (PDH) phosphorylation in A549 cells...
May 15, 2018: Free Radical Research
https://www.readbyqxmd.com/read/29763372/acetyl-coa-from-inflammation-induced-fatty-acids-oxidation-promotes-hepatic-malate-aspartate-shuttle-activity-and-glycolysis
#12
Tongxin Wang, Weilei Yao, Ji Li, Qiongyu He, Yafei Shao, Feiruo Huang
Hepatic metabolic syndrome is associated with inflammation, as it stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA. But how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS), and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins...
May 15, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29756269/genetic-and-clinical-features-of-chinese-patients-with-mitochondrial-ataxia-identified-by-targeted-next-generation-sequencing
#13
Hai-Lin Dong, Yin Ma, Quan-Fu Li, Yi-Chu Du, Lu Yang, Sheng Chen, Zhi-Ying Wu
AIM: To characterize the mutations in mitochondrial DNA (mtDNA) and mitochondrion-related nuclear genes (nDNA), and clinical features in Chinese patients with mitochondrial ataxia. METHODS: Targeted next-generation sequencing (NGS) technology was performed to screen the whole mtDNA sequence and nDNA genes in a cohort of 33 unrelated ataxia patients. RESULTS: A total of 5 pedigrees were finally genetically diagnosed as mitochondrial ataxia, with 3 pathogenic mutations (m...
May 13, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29756010/mitochondrial-protein-sulfenation-during-aging-in-the-rat-brain
#14
Xiaorong Yang, Jinzi Wu, Siqun Jing, Michael J Forster, Liang-Jun Yan
There is accumulating evidence that cysteine sulfenation (cys-SOH) in proteins plays an important role in cellular response to oxidative stress. The purpose of the present study was to identify mitochondrial proteins that undergo changes in cys-SOH during aging. Studies were conducted in rats when they were 5 or 30 months of age. Following blocking of free protein thiols with N -ethylmaleimide, protein sulfenic acids were reduced by arsenite to free thiol groups that were subsequently labeled with biotin-maleimide...
2018: Biophysics Reports
https://www.readbyqxmd.com/read/29753302/contribution-of-hepatic-retinaldehyde-dehydrogenase-induction-to-impairment-of-glucose-metabolism-by-high-fat-diet-feeding-in-c57bl-6j-mice
#15
Jiong Xu, Mian Zhang, Xiangping Zhang, Hanyu Yang, Binbin Sun, Zhongjian Wang, Yaqian Zhou, Shuting Wang, Xiaodong Liu, Li Liu
Obesity and insulin resistance are associated with overexpression of retinaldehyde dehydrogenase 1 (RALDH1). We aimed to investigate the roles of hepatic RALDH1 induction in glucose metabolism impairment using mice fed with high-fat diet (HFD). Mice were fed with HFD for 8 weeks and treated with RALDH inhibitor citral for another 4 weeks. Oral glucose tolerance test (OGTT), pyruvate tolerance test (PTT) and insulin tolerance test (ITT) were operated. Expressions of Phosphoenolpyruvate carboxykinase 1 (PCK1), glucokinase (GCK) and RALDH1 were measured...
May 12, 2018: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29753025/identification-and-efficacy-of-glycine-serine-and-threonine-metabolism-in-potentiating-kanamycin-mediated-killing-of-edwardsiella-piscicida
#16
Jin-Zhou Ye, Xiang-Min Lin, Zhi-Xue Cheng, Yu-Bin Su, Wan-Xin Li, Far-Man Ali, Jun Zheng, Bo Peng
We previously showed that glucose potentiated kanamycin to kill multidrug-resistant Edwardsiella piscicida through activation of the TCA cycle. However, whether other regulatory mechanism is involved requires further investigation. By quantitative proteomics technology, iTRAQ, we systematically mapped the altered proteins in the presence of glucose and identified 94 differentially expressed proteins. The analysis of the altered proteins by pathways, amino acid biosynthesis and metabolism were enriched. And the most significantly altered eight amino acids tyrosine, phenylalanine, valine, leucine, isoleucine, glycine, serine and threonine were investigated for their potentiation of kanamycin to kill EIB202, where glycine, serine and threonine showed the strongest efficacy than the others...
May 9, 2018: Journal of Proteomics
https://www.readbyqxmd.com/read/29752808/prenatal-sonographic-description-of-fetuses-affected-by-pyruvate-dehydrogenase-or-pyruvate-carboxylase-deficiency
#17
Olivier Picone, Charles Egloff, Aurelia Eldin de Pecoulas, Charlotte Mechler, Audrey Boutron, Isabelle Simon, Agnes Guet, Jeanne Sibiude, Laurent Mandelbrot
INTRODUCTION: Pyruvate dehydrogenase deficiency (PDHD) and pyruvate carboxylase deficiency (PCD) are diseases with severe neonatal forms, and their low prevalence makes them difficult to diagnose during pregnancy. Our objective was to describe prenatal ultrasound features that may be suggestive of these diagnoses. METHODS: We analyzed 3 cases from our institution and reviewed 12 published cases of PDHD and 6 cases of PCD, recording all of the ultrasound signs, as well as magnetic resonance (MR) findings when available...
May 12, 2018: Prenatal Diagnosis
https://www.readbyqxmd.com/read/29740212/ldh-apromotes-epithelial-mesenchymal-transition-by-upregulating-zeb2-in-intestinal-type-gastric-cancer
#18
Yongjie Zhang, Sen Lin, Yan Chen, Fei Yang, Shenlin Liu
Introduction: Epithelial-mesenchymal transition (EMT) is regarded as a crucial process of invasion and metastasis, which contribute greatly to cancer-related relapse and death. Based on research results that hypoxia can trigger gastric cancer EMT and decreasing lactate production can selectively kill hypoxic cancer cells, we infer that lactate dehydrogenase A (LDH-A) transforming pyruvate into lactate is at least in part responsible for poor prognosis of gastric cancer. Materials and methods: We used siRNA to knock down LDH-A in intestinal-type gastric cancer (ITGC) cell lines SGC7901 and BGC823...
2018: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29739849/a-novel-inhibitor-of-pyruvate-dehydrogenase-kinase-stimulates-myocardial-carbohydrate-oxidation-in-diet-induced-obesity
#19
Cheng-Yang Wu, Santhosh Satapati, Wenjun Gui, Richard M Wynn, Gaurav Sharma, Mingliang Lou, Xiangbing Qi, Shawn C Burgess, Craig Malloy, Chalermchai Khemtong, A Dean Sherry, David Chuang, Matthew E Merritt
The pyruvate dehydrogenase complex (PDC) is a key control point of energy metabolism and is subject to regulation by multiple mechanisms, including post-translational phosphorylation by pyruvate dehydrogenase kinase (PDK). Pharmacological modulation of PDC activity could provide a new treatment for diabetic cardiomyopathy, as dysregulated substrate selection is concomitant with decreased heart function. Dichloroacetate (DCA), a classic PDK inhibitor, has been used to treat diabetic cardiomyopathy, but the lack of specificity and side effects of DCA indicate a more specific inhibitor of PDK is needed...
May 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29733959/itraq-based-proteomic-profile-analysis-of-isknv-infected-cpb-cells-with-emphasizing-on-glucose-metabolism-apoptosis-and-autophagy-pathways
#20
Shiwei Wu, Lujun Yu, Xiaozhe Fu, Xi Yan, Qiang Lin, Lihui Liu, Hongru Liang, Ningqiu Li
Infectious spleen and kidney necrosis virus (ISKNV) has caused significant losses in the cultured mandarin fish (Siniperca chuatsi) industry. The molecular mechanisms that underlie interaction between ISKNV and hosts are not fully understood. In this study, the proteomic profile of CPB cells at progressive time points after ISKNV infection was analyzed by isobaric tags for relative and absolute quantitation (iTRAQ). A total of 2731 proteins corresponding to 6363 novel peptides (false discovery rate <0.01) were identified...
May 4, 2018: Fish & Shellfish Immunology
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