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51.
52.
Józef Langfort Leszek Budohoski Hanna Kaciuba-Uściłko Krystyna Nazar John R. A. Challiss Eric A. Newsholme 《European journal of applied physiology》1991,62(2):145-150
Summary The effects of two types of acute exercise (1 h treadmill running at 20 m· min–1, or 6 × 10-s periods at 43 m · min–1, 0° inclination), as well as two training regimes (endurance and sprint) on the sensitivity of epitrochlearis muscle [fast twitch (FT) fibres] to insulin were measured in vitro in rats. The hormone concentration in the incubation medium producing the half maximal stimulation of lactate (la) production and glycogen synthesis was determined and used as an index of the muscle insulin sensitivity. A single period of moderate endurance as well as the sprint-type exercise increased the sensitivity of la production to insulin although the rate of la production enhanced markedly only after sprint exercise at 10 and 100 U· ml–1 of insulin. These effects persisted for up to 2 h after the termination of exercise. Both types of exercise significantly decreased the muscle glycogen content, causing a moderate enhancement in the insulin-stimulated rates of glycogen synthesis in vitro for up to 2 h after exercise. However, a significant increase in the sensitivity of this process to insulin was found only in the muscle removed 0.25 h after the sprint effort. Training of the sprint and endurance types increased insulin-stimulated rates of glycolysis 24 h after the last period of exercise. The sensitivity of this process to insulin was also increased at this instant. Both types of training increased the basal and maximal rates of glycogen snythesis, as well as the sensitivity of this process to insulin at the 24th following the last training session. It was concluded that in the epitrochlearis muscle, containing mainly FT fibres, both moderate and intensive exercise (acute and repeated) were effective in increasing sensitivity of glucose utilization to insulin. Thus, the response in this muscle type to increased physical activity differs from that reported previously in the soleus muscle, representing the slow-twitch, oxidative fibres in which sprint exercise did not produce any changes in the muscle insulin sensitivity. 相似文献
53.
Frataxin is reduced in Friedreich ataxia patients and is associated with mitochondrial membranes 总被引:17,自引:8,他引:17
Campuzano V; Montermini L; Lutz Y; Cova L; Hindelang C; Jiralerspong S; Trottier Y; Kish SJ; Faucheux B; Trouillas P; Authier FJ; Durr A; Mandel JL; Vescovi A; Pandolfo M; Koenig M 《Human molecular genetics》1997,6(11):1771-1780
Friedreich ataxia is a progressive neurodegenerative disorder caused by
loss of function mutations in the frataxin gene. In order to unravel
frataxin function we developed monoclonal antibodies raised against
different regions of the protein. These antibodies detect a processed 18
kDa protein in various human and mouse tissues and cell lines that is
severely reduced in Friedreich ataxia patients. By immunocytofluorescence
and immunocytoelectron microscopy we show that frataxin is located in
mitochondria, associated with the mitochondrial membranes and crests.
Analysis of cellular localization of various truncated forms of frataxin
expressed in cultured cells and evidence of removal of an N-terminal
epitope during protein maturation demonstrated that the mitochondrial
targetting sequence is encoded by the first 20 amino acids. Given the
shared clinical features between Friedreich ataxia, vitamin E deficiency
and some mitochondriopathies, our data suggest that a reduction in frataxin
results in oxidative damage.
相似文献
54.
Ferrer I Kapfhammer JP Hindelang C Kemp S Troffer-Charlier N Broccoli V Callyzot N Mooyer P Selhorst J Vreken P Wanders RJ Mandel JL Pujol A 《Human molecular genetics》2005,14(23):3565-3577
ATP-binding cassette (ABC) transporters facilitate unidirectional translocation of chemically diverse substances, ranging from peptides to lipids, across cell or organelle membranes. In peroxisomes, a subfamily of four ABC transporters (ABCD1 to ABCD4) has been related to fatty acid transport, because patients with mutations in ABCD1 (ALD gene) suffer from X-linked adrenoleukodystrophy (X-ALD), a disease characterized by an accumulation of very-long-chain fatty acids (VLCFAs). Inactivation in the mouse of the abcd1 gene leads to a late-onset neurodegenerative condition, comparable to the late-onset form of X-ALD [Pujol, A., Hindelang, C., Callizot, N., Bartsch, U., Schachner, M. and Mandel, J.L. (2002) Late onset neurological phenotype of the X-ALD gene inactivation in mice: a mouse model for adrenomyeloneuropathy. Hum. Mol. Genet., 11, 499-505.]. In the present work, we have generated and characterized a mouse deficient for abcd2, the closest paralog to abcd1. The main pathological feature in abcd2-/- mice is a late-onset cerebellar and sensory ataxia, with loss of cerebellar Purkinje cells and dorsal root ganglia cell degeneration, correlating with accumulation of VLCFAs in the latter cellular population. Axonal degeneration was present in dorsal and ventral columns in spinal cord. We have identified mitochondrial, Golgi and endoplasmic reticulum damage as the underlying pathological mechanism, thus providing evidence of a disturbed organelle cross-talk, which may be at the origin of the pathological cascade. 相似文献
55.
The tongue of the white tailed eagle is elongated with a sharp-ended apex. The length of the tongue is 6 cm. The characteristic morphological features observed on the body of the tongue include a distinct median groove dividing the mucosa into two symmetrical, convex lateral parts and a single crest of large conical papillae in the posterior part of the lingual body, extending over the surface of the flat root of the tongue. The mucosa of the lingual body and root is covered by the parakeratinized multilayered epithelium. The horny layer in the mucosal epithelium was observed in the median groove, on the conical papillae and on the ventral surface of the tongue. The observations of the three dimensional structure of the subepithetial connective tissue revealed the presence of a system of laminae or smaller interconnected ridges, depending on the area of the tongue. In the white tailed eagles the anterior and posterior lingual glands were distinguished. The glands consist of several alveolar-tubular secretory units and a subepithelial chamber collecting the mucous secretion. The orifices of the anterior glands are situated on the lateral surfaces of the posterior part of the lingual body, whereas the posterior lingual glands open on the entire surface of the lingual root. 相似文献
56.
Behar D Schlesinger M Halle D Ben-Ami H Edoute Y Shahar E Kasis I Shihab S Elstein D Zimran A Mandel H 《American journal of medical genetics》2002,110(1):25-29
Deficiencies of terminal complement components, particularly the latter ones, are often detected because of increased susceptibility to Neisserial infections. Herein we document the first report of C7 deficiency among a highly inbred Arab population living in the lower Galilee region of Israel. Both biochemical and molecular analysis were performed on samples from infected survivors and parents of children who succumbed to Neisserial infections in a 4-year period. Only the index case who suffered recurrent infections and a sibling who had not suffered an infection during the outbreak were found to be C7-deficient. The mutation was found to be the one previously described to be prevalent among Israeli Jews of Moroccan ancestry (mutation G1135C). The implications of this finding are discussed in the context of family pedigree, the protective effect of complement deficiency, and the clinical outcome. 相似文献
57.
A heterogeneous set of FMR1 proteins is widely distributed in mouse tissues and is modulated in cell culture 总被引:8,自引:7,他引:8
58.
Lynch G Kohler S Leser J Beil M Garcia-Marin LJ Lutz MP 《Pflügers Archiv : European journal of physiology》2004,448(4):445-451
The aim of this study was to establish whether the rate of fatty acid (FA) incorporation and its utilization by the isolated soleus muscle is modified under conditions of thyroid hormone deficit or excess. The rate of palmitic acid (PA) uptake, oxidation and incorporation into intramuscular lipids with increasing PA concentration (0.5–1.5 mM) in the incubation medium were determined. In hypothyroid rats intramuscular triacylglycerol (TG) synthesis was increased, while the rate of PA oxidation to CO2 and incorporation into mono- and diacylglycerols (MG/DG) and phospholipids (PL) remained unchanged. In rats with triiodothyronine (T3) excess the rate of all processes studied was enhanced, although the percentage incorporation of PA into different classes of intramuscular lipids was fairly constant and, independently of thyroid state and FA concentration in the medium, was 56–66% for TG, 9-14% for MG/DG and 24–32% for PL. Our results thus indicate that even short-term T3 excess accelerates the rate of FA uptake and metabolism in the oxidative soleus muscle, whereas in hypothyroid rats only intramuscular TG synthesis is affected. 相似文献
59.
M B Veber S Cunningham-Rundles M Schulman F Mandel P A Auld 《Clinical and experimental immunology》1991,83(3):391-395
Investigation of lymphocyte activation in vitro to microbial pathogens was undertaken in very-low-birth-weight infants during the first 2 weeks of life. Twenty-three infants with birth weights less than 1500 g were studied on day 1. Normal adults (n = 23) and cord blood from seven full-term infants were used as controls. Longitudinal studies were also carried out on seven of the 23 infants 2 weeks following delivery. Results indicated that lymphocyte responses of very-low-birth-weight infants on day 1 of life were significantly greater than those of both adult controls and full-term infants, particularly to Haemophilus influenzae, Staphylococcus epidermidis and Staphylococcal protein A. In contrast, response to the T cell mitogen phytohaemagglutinin (PHA) was significantly less in very-low-birth-weight infants than in adult controls and full-term infants. The seven very-low-birth-weight infants studied showed a down-regulation of immune response in the 2 weeks following birth, such that responses on day 14 were significantly less than those on day 1 for the same activators. This shift in immune response appears to have important implications for the immune development and host defence in the post-natal period. 相似文献
60.
The initial event in the regulatory volume increase (RVI) of rat hepatocytes is an influx of Na+ that is then exchanged for K+ via stimulation of Na+/K+-adenosine triphosphatase (ATPase). In this study, we analysed the activation pattern of the Na+ transporters underlying RVI as a function of the degree of hypertonic stress. In confluent primary cultures, four hypertonic conditions were tested (changes from 300 to 327, 360, 400 or 450 mosmol/l) and the activities of Na+ conductance, Na+/H+ antiport, Na+-K+-2Cl- symport and Na+/K+-ATPase were quantified using intracellular microelectrodes, microfluorometry and time-dependent, furosemide- or ouabain-sensitive 86Rb+ uptake, respectively. Neither Na+ conductance nor Na+-K+-2Cl- symport responded to 327 mosmol/A. At 360, 400 and 450 mosmol/l, uptake via these transporters would lead to increases of cell Na+ by 33.0, 49.0 and 49.0 and by 4.5, 10.4 and 9.2 mmol/l per 10 min, respectively. In contrast, Na+/H+ antiport exhibited 65% of its maximal activation already at 327 mosmol/l. At the four osmolarities tested, this transporter would augment cell Na+ by 6.9, 8.9, 9.8 and 10.6 mmol/l per 10 min. The sums of Na+ import were consistent with the amounts of Na+ exported via Na+/K+-ATPase plus the actual increases of cell Na+ (21.2, 58.5, 63.6 and 68.3 mmol/l per 10 min and 2.2, 4.0, 6.3 and 8.2 mmol/l, respectively). In addition, these elevations of cell Na+ plus the increases of cell K+ (via Na+/K+-ATPase) that amounted to 5.0, 6.5, 17.5 and 18.4 mmol/l were consistent with the increases of intracellular osmotic (cationic) activity of 2.5, 11.5, 21.0 and 28.5 mmol/l, respectively, computed from RVI data. It is concluded that the principle of rat hepatocyte RVI, i.e. an initial uptake of Na+ that is then exchanged for K+ via Na+/K+-ATPase, is realized over the entire range of 9-50% hypertonicity tested. The set-point for the activation of RVI clearly lies below 327 mosmol/l. Na+/H+ antiport is the most sensitive Na+ importer involved in RVI, whereas Na+ conductance plays the prominent role from 360 mosmol/l upwards. 相似文献