Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.3.3.1 (citrate synthase)
 4,488 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Understanding the functional genomics and proteomics of plasmodia underpins the development of new approaches to antimalarial chemotherapy. Although genome databanks (e.g. PlasmoDB) and biocomputing tools (e.g. PlasMit, PlasmoAP, PATS) are useful in providing a global albeit predictive view of the myriad of about 5000 genes, only 40% are annotated, with few cases of endorsed subcellular localizations of the corresponding proteins in animal models. Progress in plasmodial protein trafficking has been hampered by the lack of a simple yet reliable method for studying subcellular localization of plasmodial proteins. In this study, we have used a combination of fluorescent markers, organelle-specific probes, phase contrast microscopy, and confocal microscopy to locate a selection of signal peptides from 10 plasmodial proteins in CHO-K1 cells. These eukaryotic cells serve as an in vitro living system for studying the cellular destinations of four mitochondrial-targeted TCA cycle proteins (citrate synthase, CS; isocitrate dehydrogenase, ICDH; branched chain alpha-keto-acid dehydrogenase E1alpha subunit, BCKDH; succinate dehydrogenase flavoprotein-subunit, SDH), two nuclear-targeted proteins (histone deacetylase, HDAC; RNA polymerase, RPOL), two apicoplast-targeted proteins (pyruvate kinase 2, PK2; glutamate dehydrogenase, GDH), and two cytoplasmic resident proteins (malate dehydrogenase, MDH; glycerol kinase, GK). The respective localizations of these malarial proteins have complied with the selected molecular targets, viz. mitochondrial, nuclear and cytoplasmic. Interestingly, MDH that is widely known to be resident in eukaryotic mitochondria was found to be cytoplasmic, probably due to the absence of molecular target sequences. Since the localization of plasmodial proteins is central to the authentication of their pathophysiological roles, this experimental system will serve as a useful a priori approach.
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PMID:A relevant in vitro eukaryotic live-cell system for the evaluation of plasmodial protein localization. 1683 57

An infusion of Coreopsis tinctoria (CT) flowering tops is traditionally used in Portugal to control hyperglycemia; however, the effects of CT protection against high-fat diet (HFD)-induced hepatic insulin resistance have not been systematically studied and the precise mechanism of action is not clear. The metabolomic profiles of insulin-resistant rats fed a HFD and a CT-supplemented diet (HFD supplemented with CT drinking) for 8 weeks were investigated. Serum samples for clinical biochemistry and liver samples for histopathology and liquid chromatography-mass spectrometry-based metabolomic research were collected. Western blot and quantitative real-time PCR analyses were further used to measure the expression of several relevant enzymes together with perturbed metabolic pathways. Using analysis software, the CT treatment was found to significantly ameliorate the disturbance in 10 metabolic pathways. Combined metabolomic, Western blot, and quantitative real-time PCR analyses revealed that CT treatment significantly improved the glucose homeostasis by, on the one hand, through inhibiting the expression of gluconeogenic pathway key proteins glucose-6-phosphatase and phosphoenolpyruvate carboxykinase and, on the other hand, via regulating the mRNA or protein levels of the Krebs cycle critical enzymes (citrate synthase, succinate dehydrogenase complex, subunit A, flavoprotein, and dihydrolipoamide S-succinyltransferase). These results provide metabolic evidence of the complex pathogenic mechanism involved in hepatic insulin resistance and that the supplementation with CT improves insulin resistance at a global scale. Liquid chromatography-mass spectrometry-based metabolomics approaches are helpful to further understand diabetes-related mechanisms.
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PMID:The Flower Tea Coreopsis tinctoria Increases Insulin Sensitivity and Regulates Hepatic Metabolism in Rats Fed a High-Fat Diet. 2577 55