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- Boon, Hanneke, 1981-, et al.
(författare)
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Influence of chronic and acute spinal cord injury on skeletal muscle Na+-K+-ATPase and phospholemman expression in humans
- 2012
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, MD : American Physiological Society. - 0193-1849 .- 1522-1555. ; 302:7, s. E864-E871
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Tidskriftsartikel (refereegranskat)abstract
- Na +-K +-ATPase is an integral membrane protein crucial for the maintenance of ion homeostasis and skeletal muscle contractibility. Skeletal muscle Na +-K +-ATPase content displays remarkable plasticity in response to long-term increase in physiological demand, such as exercise training. However, the adaptations in Na +-K +-ATPase function in response to a suddenly decreased and/or habitually low level of physical activity, especially after a spinal cord injury (SCI), are incompletely known. We tested the hypothesis that skeletal muscle content of Na +-K +-ATPase and the associated regulatory proteins from the FXYD family is altered in SCI patients in a manner dependent on the severity of the spinal cord lesion and postinjury level of physical activity. Three different groups were studied: 1) six subjects with chronic complete cervical SCI, 2) seven subjects with acute, complete cervical SCI, and 3) six subjects with acute, incomplete cervical SCI. The individuals in groups 2 and 3 were studied at months 1, 3, and 12 postinjury, whereas individuals with chronic SCI were compared with an able-bodied control group. Chronic complete SCI was associated with a marked decrease in [ 3H]ouabain binding site concentration in skeletal muscle as well as reduced protein content of the α 1-, α 1-, and (β1-subunit of the Na +-K +-ATPase. In line with this finding, expression of the Na +-K +-ATPase α 1-, α 1- subunits progressively decreased during the first year after complete but not after incomplete SCI. The expression of the regulatory protein phospholemman (PLM or FXYD1) was attenuated after complete, but not incomplete, cervical SCI. In contrast, FXYD5 was substantially upregulated in patients with complete SCI. In conclusion, the severity of the spinal cord lesion and the level of postinjury physical activity in patients with SCI are important factors controlling the expression of Na +-K +-ATPase and its regulatory proteins PLM and FXYD5. © 2012 the American Physiological Society.
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| 2. |
- Boon, Hanneke, 1981-, et al.
(författare)
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MicroRNA-208b progressively declines after spinal cord injury in humans and is inversely related to myostatin expression
- 2015
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Ingår i: Physiological Reports. - Chichester : John Wiley & Sons. - 2051-817X. ; 3:11
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Tidskriftsartikel (refereegranskat)abstract
- The effects of long‐term physical inactivity on the expression of microRNAs involved in the regulation of skeletal muscle mass in humans are largely unknown. MicroRNAs are short, noncoding RNAs that fine‐tune target expression through mRNA degradation or by inhibiting protein translation. Intronic to the slow, type I, muscle fiber type genes MYH7 and MYH7b, microRNA‐208b and microRNA‐499‐5p are thought to fine‐tune the expression of genes important for muscle growth, such as myostatin. Spinal cord injured humans are characterized by both skeletal muscle atrophy and transformation toward fast‐twitch, type II fibers. We determined the expression of microRNA‐208b, microRNA‐499‐5p, and myostatin in human skeletal muscle after complete cervical spinal cord injury. We also determined whether these microRNAs altered myostatin expression in rodent skeletal muscle. A progressive decline in skeletal muscle microRNA‐208b and microRNA‐499‐5p expression occurred in humans during the first year after spinal cord injury and with long‐standing spinal cord injury. Expression of myostatin was inversely correlated with microRNA‐208b and microRNA‐499‐5p in human skeletal muscle after spinal cord injury. Overexpression of microRNA‐208b in intact mouse skeletal muscle decreased myostatin expression, whereas microRNA‐499‐5p was without effect. In conclusion, we provide evidence for an inverse relationship between expression of microRNA‐208b and its previously validated target myostatin in humans with severe skeletal muscle atrophy. Moreover, we provide direct evidence that microRNA‐208b overexpression decreases myostatin gene expression in intact rodent muscle. Our results implicate that microRNA‐208b modulates myostatin expression and this may play a role in the regulation of skeletal muscle mass following spinal cord injury. © 2015 The Authors
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| 3. |
- Hjeltnes, Nils
(författare)
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Physical exercise and electrical stimulation in the management of metabolic, cardiovascular and skeletal-muscle alterations in people with tetraplegia
- 1998
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Interruption of the spinal cord at the cervical level leads to permanent extensive motor paralysis, serious autonomic regulation deficits and profound short term and long term metabolic disorders. The defects play a decisive role for the tetraplegic individuals future function and health. The aims of the present thesis were (1) to assess the physical endurance capacity and the trainability of recently spinal cord injured patients, with a special emphasis on tetraplegic persons, (2) to investigate the autonomic regulatory defects during arm ergometry in chronic tetraplegic individuals, (3) to study skeletal muscle metabolic and morphologic consequences of long standing tetraplegia, and (4) to investigate the effects of electrically stimulated leg cycle training (ESLC training) on oxygen uptake, body composition, skeletal muscle glucose metabolism, and skeletal muscle morphology. To address the aims, peak VO2 was measured by conventional methods. Blood pressure was recorded by an intra-arterial method. Arterial concentrations of catecholamines were analysed by a single isotope radio-enzymatic method. Body composition was recorded by the DEXA method. Whole body peripheral insulin mediated glucose uptake was investigated by the hyperinsulinemic euglycemic clamp method. An open muscle biopsy technique combined with in vitro incubation of isolated muscle strips was used to study glucose transport in the decentralised vastus lateralis skeletal muscle. Protein expression of the glucose transporter protein (GLUT4), hexokinase (HKII), glycogen synthase (GS), and phosphofructokinase (PFK) was assessed before and after ESLC training using Western blot analysis. Corresponding enzymatic activities plus citrate synthase activity were also determined. Muscle fiber type distribution was determined by the ATP-ase staining method, capillary supply by the PAS method, and glycogen by an enzymatic method. Peak VO2 in tetraplegic subjects was very low due to limited volatile arm muscles and weak sympathetic exercise response. Arm ergometry training did not improve the metabolic indicator of aerobic capacity, peak V02, in tetraplegic persons. ESLC training increased peak VO2 by 70%, and led to further improvements in body composition. Whole body insulin mediated glucose uptake was increased by 30% in tetraplegic persons after ESLC training. The improvement in glucose uptake occurred concomitant with a two-fold increase in basal and insulin-stimulated in vitro muscle glucose transport and an increase in lean body mass. ESLC training increased muscle glycogen stores by 68%, and induced profound overexpression of GLUT4, HKII, and GS in all the tetraplegic subjects, whereas PFK expression was increased in four of five persons following training. Taken together, the results provide the first evidence for a direct connection between overexpression of key enzymes in glucose metabolism through exercise (ESLC) to enhanced glucose transport and metabolism in human skeletal muscle. Muscle biopsies from tetraplegic individuals demonstrated extensive muscle fiber atrophy, increased connective tissue and large dominance of type llb fibers. Following 8 wks of ESLC training, the histological profile of the muscle fibers was not significantly altered. Furthermore training did not lead to increases in the fiber cross sectional area. However, type llb fiber dominance was reduced. In four of five tetraplegic persons, an increased proportion of type lla fibers and a small increase in type I fibers was noted following training. In conclusion, cervical spinal cord injury leads to physical inactivity, which accounts for profound changes in metabolism and morphology, which may increase the risk for long-term complications such as non-insulin dependent diabetes mellitus or cardiovascular disease. ESLC training activates large decentralised muscle groups, and thereby normalises the metabolic disturbances associated with spinal injury. Thus, ESLC training is highly recommended for both the early and late stages after spinal cord injuries.
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| 4. |
- Kostovski, Emil, et al.
(författare)
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Altered content of AMP-activated protein kinase isoforms in skeletal muscle from spinal cord injured subjects
- 2013
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - Bethesda, MD : American Physiological Society. - 0193-1849 .- 1522-1555. ; 305:9, s. E1071-E1080
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Tidskriftsartikel (refereegranskat)abstract
- AMP-activated protein kinase (AMPK) is a pivotal regulator of energy homeostasis. Although downstream targets of AMPK are widely characterized, the physiological factors governing isoform expression of this protein kinase are largely unknown. Nerve/contractile activity has a major impact on the metabolic phenotype of skeletal muscle, therefore likely to influence AMPK isoform expression. Spinal cord injury represents an extreme form of physical inactivity, with concomitant changes in skeletal muscle metabolism. We assessed the influence of longstanding and recent spinal cord injury on protein abundance of AMPK isoforms in human skeletal muscle. We also determined muscle fiber type as a marker of glycolytic or oxidative metabolism. In subjects with longstanding complete injury, protein abundance of the AMPKγ3 subunit, as well as myosin heavy chain (MHC) IIa and IIx, were increased, whereas abundance of the AMPKγ1 subunit and MHC I were decreased. Similarly, abundance of AMPKγ3 and MHC IIa proteins were increased, whereas AMPKα2, -β1, and -γ1 subunits and MHC I abundance was decreased during the first year following injury, reflecting a more glycolytic phenotype of the skeletal muscle. However, in incomplete cervical lesions, partial recovery of muscle function attenuated the changes in the isoform profile of AMPK and MHC. Furthermore, exercise training (electrically stimulated leg cycling) partly normalized mRNA expression of AMPK isoforms. Thus, physical activity affects the relative expression of AMPK isoforms. In conclusion, skeletal muscle abundance of AMPK isoforms is related to physical activity and/or muscle fiber type. Thus, physical/neuromuscular activity is an important determinant of isoform abundance of AMPK and MCH. This further underscores the need for physical activity as part of a treatment regimen after spinal cord injury to maintain skeletal muscle metabolism. © 2013 the American Physiological Society.
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| 5. |
- Long, Yun Chau, et al.
(författare)
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Differential expression of metabolic genes essential for glucose and lipid metabolism in skeletal muscle from spinal cord injured subjects
- 2011
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Ingår i: Journal of applied physiology. - Bethesda, MD : American Physiological Society. - 8750-7587 .- 1522-1601. ; 110:5, s. 1204-1210
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Tidskriftsartikel (refereegranskat)abstract
- Skeletal muscle plays an important role in the regulation of energy homeostasis; therefore, the ability of skeletal muscle to adapt and alter metabolic gene expression in response to changes in physiological demands is critical for energy balance. Individuals with cervical spinal cord lesions are characterized by tetraplegia, impaired thermoregulation, and altered skeletal muscle morphology. We characterized skeletal muscle metabolic gene expression patterns, as well as protein content, in these individuals to assess the impact of spinal cord injury on critical determinants of skeletal muscle metabolism. Our results demonstrate that mRNA levels and protein expression of skeletal muscle genes essential for glucose storage are reduced, whereas expression of glycolytic genes is reciprocally increased in individuals with spinal cord injury. Furthermore, expression of genes essential for lipid oxidation is coordinately reduced in spinal cord injured subjects, consistent with a marked reduction of mitochondrial proteins. Thus spinal cord injury resulted in a profound and tightly coordinated change in skeletal muscle metabolic gene expression program that is associated with the aberrant metabolic features of the tissue. © 2011 the American Physiological Society.
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