5 results on '"Mehan KA"'
Search Results
2. Pyruvate dehydrogenase activation and kinase expression in human skeletal muscle during fasting.
- Author
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Spriet LL, Tunstall RJ, Watt MJ, Mehan KA, Hargreaves M, and Cameron-Smith D
- Subjects
- Adult, Base Sequence, DNA Primers, Enzyme Activation, Female, Humans, Isoenzymes genetics, Male, Muscle, Skeletal enzymology, Protein Serine-Threonine Kinases, Pyruvate Dehydrogenase Acetyl-Transferring Kinase, RNA, Messenger genetics, Fasting physiology, Muscle, Skeletal physiology, Protein Kinases genetics, Pyruvate Dehydrogenase Complex metabolism
- Abstract
Fasting forces adaptive changes in whole body and skeletal muscle metabolism that increase fat oxidation and decrease the oxidation of carbohydrate. We tested the hypothesis that 40 h of fasting would decrease pyruvate dehydrogenase (PDH) activity and increase PDH kinase (PDK) isoform mRNA expression in human skeletal muscle. The putative transcriptional activators of PDK isozymes, peroxisome proliferator-activated receptor-alpha (PPAR-alpha) protein, and forkhead homolog in rhabdomyosarcoma (FKHR) mRNA were also measured. Eleven healthy adults fasted after a standard meal (25% fat, 60% carbohydrate, 15% protein) with blood and skeletal muscle samples taken at 3, 15, and 40 h postprandial. Fasting increased plasma free fatty acid, glycerol, and beta-hydroxybutyrate concentrations and decreased glucose and insulin concentrations. PDH activity decreased from 0.88 +/- 0.11 mmol acetyl-CoA. min(-1). kg wet muscle wt(-1) at 3 h to 0.62 +/- 0.10 (P = not significant) and 0.39 +/- 0.06 (P < 0.05) mmol. min(-1). kg wet mass(-1) after 15 and 40 h of fasting. Although all four PDK isoforms were expressed in human skeletal muscle, PDK-2 and -4 mRNA were the most abundant. PDK-1 and -3 mRNA abundance was approximately 1 and 15% of the PDK-2 and -4 levels, respectively. The 40-h fast had no effect on PDK-1, -2, and -3 mRNA expression. PDK-4 mRNA was significantly increased approximately 3-fold after 15 h and approximately 14-fold after 40 h of fasting. Skeletal muscle PPAR-alpha protein and FKHR mRNA abundance were unaffected by the fast. The results suggest that decreased PDH activation after 40 h of fasting may have been a function of the large increase in PDK-4 mRNA expression and possible subsequent increase in PDK protein and activity. The changes in PDK-4 expression and PDH activity did not coincide with increases in the transcriptional activators PPAR-alpha and FKHR.
- Published
- 2004
- Full Text
- View/download PDF
3. Human skeletal muscle creatine transporter mRNA and protein expression in healthy, young males and females.
- Author
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Murphy RM, Tunstall RJ, Mehan KA, Cameron-Smith D, McKenna MJ, Spriet LL, Hargreaves M, and Snow RJ
- Subjects
- Adolescent, Adult, Female, Humans, Immunohistochemistry, Male, Microscopy, Fluorescence, Muscles pathology, Phosphates, RNA metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sex Factors, Transcription, Genetic, Membrane Transport Proteins metabolism, Muscle, Skeletal metabolism, RNA, Messenger metabolism
- Abstract
The present study investigated whether there were any differences between males and females in respect to creatine transporter (CreaT) gene expression and/or total creatine (TCr) content in human vastus lateralis muscle. Skeletal muscle obtained from young healthy male (n = 13, age: 23.2 +/- 5.0 years) and female subjects (n = 12, age: 21.7 +/- 4.3 years) was analyzed for CreaT mRNA, CreaT protein and TCr content. Total CreaT protein content in the muscle was similar (p > 0.05) between the sexes. Two bands (approximately 55 and 73 kDa) of the CreaT protein were detected in all muscle samples. Both the 55 and the 73 kDa bands were present in similar (p > 0.05) amounts in males compared with females. The 73 kDa band was in greater abundance (p < 0.05) than the 55 kDa band, irrespective of gender. In addition, CreaT mRNA expression relative to beta-actin mRNA and the TCr content (males: 117.8 +/- 2.2, females: 125.3 +/- 4.3 mmol.kg(-1) dry mass) were also unaffected (p > 0.05) by gender. These data demonstrate that gender does not influence skeletal muscle TCr content and CreaT gene expression in young human subjects.
- Published
- 2003
4. Exercise training increases lipid metabolism gene expression in human skeletal muscle.
- Author
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Tunstall RJ, Mehan KA, Wadley GD, Collier GR, Bonen A, Hargreaves M, and Cameron-Smith D
- Subjects
- 3-Hydroxyacyl CoA Dehydrogenases genetics, 3-Hydroxyacyl CoA Dehydrogenases metabolism, Adult, CCAAT-Enhancer-Binding Proteins genetics, CCAAT-Enhancer-Binding Proteins metabolism, CD36 Antigens, Carnitine O-Palmitoyltransferase genetics, Carnitine O-Palmitoyltransferase metabolism, Carrier Proteins genetics, Carrier Proteins metabolism, DNA-Binding Proteins genetics, DNA-Binding Proteins metabolism, Exercise Test, Fatty Acid-Binding Protein 7, Fatty Acid-Binding Proteins, Female, Humans, Male, Membrane Glycoproteins genetics, Membrane Glycoproteins metabolism, Organic Anion Transporters genetics, Organic Anion Transporters metabolism, RNA, Messenger metabolism, Receptors, Cytoplasmic and Nuclear genetics, Receptors, Cytoplasmic and Nuclear metabolism, Sterol Regulatory Element Binding Protein 1, Time Factors, Transcription Factors genetics, Transcription Factors metabolism, Exercise physiology, Gene Expression Regulation physiology, Lipid Metabolism, Muscle, Skeletal metabolism, Neoplasm Proteins, Tumor Suppressor Proteins
- Abstract
The effects of a single bout of exercise and exercise training on the expression of genes necessary for the transport and beta-oxidation of fatty acids (FA), together with the gene expression of transcription factors implicated in the regulation of FA homeostasis were investigated. Seven human subjects (3 male, 4 female, 28.9 +/- 3.1 yr of age, range 20-42 yr, body mass index 22.6 kg/m(2), range 17-26 kg/m(2)) underwent a 9-day exercise training program of 60 min cycling per day at 63% peak oxygen uptake (VO(2 peak); 104 +/- 14 W). On days 1 and 9 of the program, muscle biopsies were sampled from the vastus lateralis muscle at rest, at the completion of exercise, and again 3 h postexercise. Gene expression of key components of FA transport [FA translocase (FAT/CD36), plasma membrane-associated FA-binding protein], beta-oxidation [carntine palmitoyltransferase(CPT) I, beta-hydroxyacyl-CoA dehydrogenase] and transcriptional control [peroxisome proliferator-activated receptor (PPAR)alpha, PPAR gamma, PPAR gamma coactivator 1, sterol regulatory element-binding protein-1c] were unaltered by exercise when measured at the completion and at 3 h postexercise. Training increased total lipid oxidation by 24% (P < 0.05) for the 1-h cycling bout. This increased capacity for lipid oxidation was accompanied by an increased expression of FAT/CD36 and CPT I mRNA. Similarly, FAT/CD36 protein abundance was also upregulated by exercise training. We conclude that enhanced fat oxidation after exercise training is most closely associated with the genes involved in regulating FA uptake across the plasma membrane (FAT/CD36) and across the mitochondrial membrane (CPT I).
- Published
- 2002
- Full Text
- View/download PDF
5. Fasting activates the gene expression of UCP3 independent of genes necessary for lipid transport and oxidation in skeletal muscle.
- Author
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Tunstall RJ, Mehan KA, Hargreaves M, Spriet LL, and Cameron-Smith D
- Subjects
- Adaptation, Physiological physiology, Adult, Biological Transport physiology, Blood Glucose, Carrier Proteins genetics, Fatty Acids, Nonesterified blood, Female, Glycerol blood, Humans, Insulin blood, Ion Channels, Male, Mitochondrial Proteins, Muscle, Skeletal chemistry, Oxidation-Reduction, RNA, Messenger analysis, RNA, Messenger metabolism, Reference Values, Time Factors, Transcription Factors genetics, Transcription Factors metabolism, Uncoupling Protein 3, Carrier Proteins metabolism, Fasting metabolism, Gene Expression Regulation physiology, Lipid Metabolism, Muscle, Skeletal metabolism
- Abstract
Fasting triggers a complex array of adaptive metabolic and hormonal responses including an augmentation in the capacity for mitochondrial fatty acid (FA) oxidation in skeletal muscle. This study hypothesized that this adaptive response is mediated by increased mRNA of key genes central to the regulation of fat oxidation in human skeletal muscle. Fasting dramatically increased UCP3 gene expression, by 5-fold at 15 h and 10-fold at 40 h. However the expression of key genes responsible for the uptake, transport, oxidation, and re-esterification of FA remained unchanged following 15 and 40 h of fasting. Likewise there was no change in the mRNA abundance of transcription factors. This suggests a unique role for UCP3 in the regulation of FA homeostasis during fasting as adaptation to 40 h of fasting does not require alterations in the expression of other genes necessary for lipid metabolism., ((c) 2002 Elsevier Science (USA).)
- Published
- 2002
- Full Text
- View/download PDF
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