Chang Keun Kim

Influence of β-alanine supplementation on skeletal muscle carnosine concentrations and high intensity cycling capacity

Summary.Muscle carnosine synthesis is limited by the availability of β-alanine. Thirteen male subjects were supplemented with β-alanine (CarnoSyn™) for 4 wks, 8 of these for 10 wks. A biopsy of the vastus lateralis was obtained from 6 of the 8 at 0, 4 and 10 wks. Subjects undertook a cycle capacity test to determine total work done (TWD) at 110% (CCT110%) of their maximum power (Wmax). Twelve matched subjects received a placebo. Eleven of these completed the CCT110% at 0 and 4 wks, and 8, 10 wks. Muscle biopsies were obtained from 5 of the 8 and one additional subject. Muscle carnosine was significantly increased by +58.8% and +80.1% after 4 and 10 wks β-alanine supplementation. Carnosine, initially 1.71 times higher in type IIa fibres, increased equally in both type I and IIa fibres. No increase was seen in control subjects. Taurine was unchanged by 10 wks of supplementation. 4 wks β-alanine supplementation resulted in a significant increase in TWD (+13.0%); with a further +3.2% increase at 10 wks. TWD was unchanged at 4 and 10 wks in the control subjects. The increase in TWD with supplementation followed the increase in muscle carnosine.

Effect of exercise training on muscle glucose transporter 4 protein and intramuscular lipid content in elderly men with impaired glucose tolerance

This study determined the effects of exercise training on adaptations of skeletal muscle including fibre composition, capillarity, intra-muscular triglyceride concentration (IMTG), as well as glucose transporter 4 protein (GLUT4) and metabolic enzyme activities. Percutaneous muscle biopsies from the vastus lateralis muscle were obtained from non-obese elderly Korean men (n=10; age range 58–67 years) with impaired glucose tolerance. Subjects performed 12 weeks of endurance exercise training (60–70% of the heart rate reserve). The training program improved the total GLUT4 protein expression (P<0.01), decreased the IMTG, increased the fatty acid oxidation capacity, and the number of capillaries around type 1 fibres (P<0.05), whereas no significant alteration was observed around type II fibres. All data are presented as the means together with the standard deviation. The results suggest that endurance training evokes morphological and biochemical changes in the skeletal muscle of elderly men with impaired glucose tolerance that may be considered to limit the development of type 2 diabetes.

Endoplasmic reticulum stress markers and ubiquitin–proteasome pathway activity in response to a 200-km run.

PURPOSE This study investigated whether a 200-km run modulates signaling pathways implicated in cellular stress in skeletal muscle, with special attention paid to the endoplasmic reticulum (ER) stress and to the activation of the ubiquitin-proteasome pathway. METHODS Eight men ran 200 km (28 h 03 min ± 2 h 01 min). Two muscle biopsies were obtained from the vastus lateralis muscle 2 wk before and 3 h after the race. Mitogen-activated protein kinase, ubiquitin-proteasome pathway, ER stress, inflammation, and oxidative stress markers were assayed by Western blot analysis or by quantitative real-time polymerase chain reaction. Chymotrypsin-like activity of the proteasome was measured by a fluorimetric assay. RESULTS Phosphorylation states of extracellular signal-related kinase 1/2 (+401% ± 173.8%, P = 0.027) and c-Jun N-terminal (+149% ± 61.9%, P = 0.023) increased after the race, whereas p38 phosphorylation remained unchanged. Increases in BiP (+235% ± 94.7%, P = 0.021) and in the messenger RNA level of total (+138% ± 31.2%, P = 0.002) and spliced X-box binding protein 1 (+241% ± 53.3%, P = 0.001) indicated the presence of ER stress. Transcripts of inflammatory markers interleukin-6 (+403% ± 96.1%, P = 0.002) and tumor necrosis factor-α (+233% ± 58.4%, P = 0.003) as well as oxidative stress markers metallothionein 1F (+519% ± 258.3%, P = 0.042), metallothionein 1H (+666% ± 157.5%, P = 0.002), and nicotinamide adenine dinucleotide phosphate-oxidase (NADPH oxidase) (+162% ± 60.5%, P = 0.016) were increased. The messenger RNA level of the ubiquitin ligases muscle-specific RING finger 1 (+583% ± 244.3%, P = 0.024) and muscle atrophy F-box (+249% ± 83.8%, P = 0.011) and the C2 proteasome subunit (+116% ± 40.6%, P = 0.012) also increased. Surprisingly, the amount of ubiquitin-conjugated proteins and the chymotrypsin-like activity of the proteasome were decreased by 20% ± 8.3% (P = 0.025) and 21% ± 4.4% (P = 0.001), respectively. The expression of ubiquitin-specific protease 28 deubiquitinase was increased (+81% ± 37.9%, P = 0.034). CONCLUSIONS In the skeletal muscle, a 200-km run activates the expression of ubiquitin ligases muscle-specific RING finger 1 and muscle atrophy F-box as well as various cellular stresses, among which are ER stress, oxidative stress, and inflammation. Meanwhile, compensatory mechanisms seem also triggered: the unfolded protein response is up-regulated, and the chymotrypsin-like activity of the proteasome is repressed.

Exercise type and muscle fiber specific induction of caveolin-1 expression for insulin sensitivity of skeletal muscle

It is well known that exercise can have beneficial effects on insulin resistance by activation of glucose transporter. Following up our previous report that caveolin-1 plays an important role in glucose uptake in L6 skeletal muscle cells, we examined whether exercise alters the expression of caveolin-1, and whether exercise-caused changes are muscle fiber and exercise type specific. Fifity week-old Sprague Dawley (SD) rats were trained to climb a ladder and treadmill for 8 weeks and their soleus muscles (SOL) and extensor digitorum longus muscles (EDL) were removed after the last bout of exercise and compared with those from non-exercised animals. We found that the expression of insulin related proteins and caveolins did not change in SOL muscles after exercise. However, in EDL muscles, the expression of insulin receptor β (IRβ) and glucose transporter-4 (GLUT-4) as well as phosphorylation of AKT and AMPK increased with resistance exercise but not with aerobic exercise. Also, caveolin-1 and caveolin-3 increased along with insulin related proteins only in EDL muscles by resistance exercise. These results suggest that upregulation of caveolin-1 in the skeletal muscle is fiber specific and exercise type specific, implicating the requirement of the specific mode of exercise to improve insulin sensitivity.

Erythropoietin, 2,3 DPG, oxygen transport capacity, and altitude training in adolescent Alpine skiers.

BACKGROUND Rapid growth during adolescence caused by metabolic changes and their metabolic response to anaerobic and aerobic exercise differs considerably from that in adults and this is especially true in the responses to stresses, such as altitude exposure. However, there is little information on the suitability of exercise training at altitude for young athletes. METHODS Six male Korean adolescent alpine skiers (13-17 yr), with a skiing career of 3-5 yr, participated in the study. All subjects were exposed to an altitude of 2700 m (8858 ft) for 5 wk and altitude exposure consisted of 6 d/wk of training (4-5 h/d), with living quarters at 2100 m (-6890 ft) (Tignes, France). The 5 wk of ski training at altitude were maintained at the same level (the same number of slalom and giant slalom skiing trials) as at sea level. RESULTS There was a significant increase in oxygen transport capacity, despite decreased erythropoietin (EPO) production (-31%) after altitude training. Red blood cell (RBC), hemoglobin (Hb), hematocrit (Hct), and 2,3 DPG concentrations increased significantly during altitude exposure and after return to sea level. DISCUSSION Results indicate that applying altitude training in adolescent skiers may improve their endurance performance. However, EPO production during altitude training needs to be evaluated in larger future studies.

Creatine kinase isoenzyme activity during and after an ultra-distance (200 km) run

It is commonly assumed that creatine kinase (CK) activity in plasma is related to the state of an inflammatory response at 24-48 h, and also it has shown biphasic patterns after a marathon run. No information is available on CK isoenzymes after an ultra-marathon run. The purpose of the present study is to examine the CK isoenzymes after a 200 km ultra-marathon run and during the subsequent recovery. Blood samples were obtained during registration 1 2 h before the 200-km race and during the race at 100 km, 150 km and at the end of 200 km, as well as after a 24 h period of recovery. Thirty-two male ultra-distance runners participated in the study. Serum CPK showed a marked increase throughout the race and 24 h recovery period (p < 0.001). Serum CK during the race occurs mostly in the CK-MM isoform and only minutely in the CK-MB isoform and is unchanged in the CK-BB isoform. High-sensitivity C-reactive protein (hs-CRP), oestradiol, AST and ALT increased significantly from the pre-race value at 100 km and a further increase took place by the end of the 200 km run. The results of our study demonstrate a different release pattern of creatine kinase after an ultra-distance (200 km) run compared to the studies of marathon running and intense eccentric exercise, and changes in several biomarkers, indicative of muscle damage during the race, were much more pronounced during the latter half (100–200 km) of the race. However, the increases in plasma concentration of muscle enzymes may reflect not only structural damage, but also their rate of clearance.

THE EFFECT OF RESISTANCE AND ENDURANCE EXERCISE TRAINING ON MUSCLE PROTEOME EXPRESSION IN HUMAN SKELETAL MUSCLE

To investigate the effect of resistance and endurance training on muscle proteome expression, samples of vastus lateralis from 10 physically active young men were analysed by 2-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Differential patterns of protein expression were determined after 4 weeks of endurance or resistance exercise training. Following endurance exercise training, carbonic anhydrase III immunoglobulin heavy chain, myosin heavy chain 1, titin, chromosome 12, and fructose-1,6-bisphosphatase 2 were up-regulated while pyruvate kinase 3 isoform, ubiquitin carboxyl-terminal hydrolase, and phosphoglucomutase were down-regulated. After the 4 weeks of resistance exercise training, five proteins, apolipoprotein A-IV precursor, microtubule-actin cross linking factor 1, myosin light chain, growth hormone inducible transmembrane protein, and an unknown protein were up-regulated and pyruvate kinase 3 isoform, human albumin, and enolase 3 were down-regulated. We conclude that endurance and resistance exercise training differently alter the expression of individual muscle proteins, and that the response of muscle protein expression may be associated with specific myofibre adaptations to exercise training. Proteomic studies represent one of the developing techniques of metabolism which may substantially contribute to new insights into muscle and exercise physiology.