Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.1.1 (hexokinase)
 5,274 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Clenbuterol, a beta2-adrenergic-receptor agonist, is known to provoke muscle hypertrophy and a slow-to-fast phenotype change. A more glycolytic phenotype should be paralleled by changes in muscle glycolytic metabolism. Two groups (n=16 for each) of 3-month-old male Wistar rats (UCL: untrained clenbuterol, and ECL: exercised clenbuterol) received a chronic administration of clenbuterol (2 mg/kg body weight/day). Two other groups of animals (U: untrained and E: exercised), were given a 0.9% NaCl solution instead of clenbuterol. E and ECL animals followed an 8-week progressive isometric force strength-training program. Both clenbuterol administration and training resulted in an increase in extensor digitorum longus (EDL) mass despite the fact that this muscle was indirectly mobilised during isometric force strength training. Clenbuterol and training induced a consistent slow-to-fast phenotype change without drastically increasing specific activities of glycolytic enzymes. Except for GAPDH and hexokinase, modifications in glycolytic-enzyme-specific activities were not explained by transcriptional changes. Lactate dehydrogenase activity was not affected by clenbuterol but was strongly augmented by training. In EDL of ECL rats, both treatments presented an opposite effect compensating each other. GLUT1 mRNA expression was augmented in EDL of UCL and ECL animals, whereas monocarboxylate transporter 1 mRNA amounts were decreased in EDL of UCL rats. Citrate synthase activity was reduced by clenbuterol treatment but remained unchanged in EDL of E animals. Creatine kinase activity was enhanced only by clenbuterol alone. These data show that clenbuterol-induced muscle hypertrophy and slow-to-fast phenotype changes are not associated with a glycolytic-enzyme-activity increase. They also suggest that in EDL isometric force strength training can reverse clenbuterol-induced molecular adaptations.
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PMID:Molecular impact of clenbuterol and isometric strength training on rat EDL muscles. 1709 70

Increasing evidence demonstrates that the hexokinase inhibitor 3-bromopyruvate (3-BrPA) induces the cell apoptotic death by inhibiting ATP generation in human cancer cells. Interestingly, some tumor cell lines are less sensitive to 3-BrPA-induced apoptosis than others. Moreover, the molecular mechanism of 3-BrPA-trigged apoptosis is unclear. In the present study, we examined the effects of 3-BrPA on the viability of the breast cancer cell lines MDA-MB-231 and MCF-7. We further investigated the potential roles of monocarboxylate transporter 1 (MCT1) in drug accumulation and efflux of breast cancer cells. Finally, we explored whether 3-BrPA enhanced daunorubicin (DNR)-induced cytotoxicity through regulation of MCT1 in breast cancer cells. MTT and colony formation assays were used to measure cell viability. Western blot analysis, flow cytometric analysis and fluorescent microscopy were used to determine the molecular mechanism of actions of MCT1 in different breast cancer cell lines. Whole-body bioluminescence imaging was used to investigate the effect of 3-BrPA in vivo. We found that 3-BrPA significantly inhibited cell growth and induced apoptosis in MCF-7 cell line, but not in MDA-MB-231 cells. Moreover, we observed that 3-BrPA efficiently enhanced DNR-induced cytotoxicity in MCF-7 cells by inhibiting the activity of ATP-dependent efflux pumps. We also found that MCT1 overexpression increased the efficacy of 3-BrPA in MDA-MB-231 cells. 3-BrPA markedly suppressed subcutaneous tumor growth in combination with DNR in nude mice implanted with MCF-7 cells. Lastly, our whole-body bioluminescence imaging data indicated that 3-BrPA promoted DNR accumulation in tumors. These findings collectively suggest that 3-BrPA enhanced DNR antitumor activity in breast cancer cells involved MCT-1, suggesting that inhibition of glycolysis could be an effective therapeutic approach for breast cancer treatment.
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PMID:3-bromopyruvate enhanced daunorubicin-induced cytotoxicity involved in monocarboxylate transporter 1 in breast cancer cells. 2660 75

Muscle respiratory capacity decides the amount of exertion one's skeletal muscle can undergo, and endurance exercise is believed to increase it. There are also certain preconditioning methods by which muscle respiratory and exercise performance can be enhanced. In this study, preconditioning with ethyl 3,4-dihydroxybenzoate (EDHB), a prolyl hydroxylase domain enzyme inhibitor, has been investigated to determine its effect on aerobic metabolism and bioenergetics in skeletal muscle, thus facilitating boost in physical performance in a rat model. We observed that EDHB supplementation increases aerobic metabolism via upregulation of HIF-mediated GLUT1 and GLUT4, thus enhancing glucose uptake in muscles. There was also a twofold rise in the activity of enzymes of tricarboxylic acid (TCA) cycle and glycolysis, ie, hexokinase and phosphofructokinase. There was an increase in citrate synthase and succinate dehydrogenase activity, resulting in the rise in the levels of ATP due to enhanced Krebs cycle activity as substantiated by enhanced acetyl-CoA levels in EDHB-treated rats as compared to control group. Increased lactate dehydrogenase activity, reduced expression of monocarboxylate transporter 1, and increase in monocarboxylate transporter 4 suggest transport of lactate from muscle to blood. There was a concomitant decrease in plasma lactate, which might be due to enhanced transport of lactate from blood to the liver. This was further supported by the rise in liver pyruvate levels and liver glycogen levels in EDHB-supplemented rats as compared to control rats. These results suggest that EDHB supplementation leads to improved physical performance due to the escalation of aerobic respiration quotient, ie, enhanced muscle respiratory capacity.
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PMID:Preconditioning with ethyl 3,4-dihydroxybenzoate augments aerobic respiration in rat skeletal muscle. 2780 May 13

Schizophrenia is a devastating illness that affects over 2 million people in the United States and costs society billions of dollars annually. New insights into the pathophysiology of schizophrenia are needed to provide the conceptual framework to facilitate development of new treatment strategies. We examined bioenergetic pathways in the dorsolateral prefrontal cortex (DLPFC) of subjects with schizophrenia and control subjects using western blot analysis, quantitative real-time polymerase chain reaction, and enzyme/substrate assays. Laser-capture microdissection-quantitative polymerase chain reaction was used to examine these pathways at the cellular level. We found decreases in hexokinase (HXK) and phosphofructokinase (PFK) activity in the DLPFC, as well as decreased PFK1 mRNA expression. In pyramidal neurons, we found an increase in monocarboxylate transporter 1 mRNA expression, and decreases in HXK1, PFK1, glucose transporter 1 (GLUT1), and GLUT3 mRNA expression. These results suggest abnormal bioenergetic function, as well as a neuron-specific defect in glucose utilization, in the DLPFC in schizophrenia.
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PMID:Neuron-specific deficits of bioenergetic processes in the dorsolateral prefrontal cortex in schizophrenia. 2949 48