Habitual exercise program protects murine intestinal, skeletal, and cardiac muscles against aging

Aging and aerobic exercise are two conditions known to interfere with health and quality of life, most likely by inducing oxidative stress to the organism. We studied the effects of aging on the morphological and functional properties of skeletal, cardiac, and intestinal muscles and their corresponding oxidative status in C57BL/6 mice and investigated whether a lifelong moderate exercise program would exert a protective effect against some deleterious effects of aging. As expected, aged animals presented a significant reduction of physical performance, accompanied by a decrease of gastrocnemius cross-sectional area and cardiac hypertrophy. However, most interesting was that aging dramatically interfered with the intestinal structure, causing a significant thickening of the ileum muscular layer. Senescent intestinal myocytes displayed many mitochondria with disorganized cristae and the presence of cytosolic lamellar corpuscles. Lipid peroxidation of ileum and gastrocnemius muscle, but not of the heart, increased in aged mice, thus suggesting enhanced oxidative stress. With exception of the intestinal muscle responsiveness, animals submitted to a daily session of 60 min, 5 days/wk, at 13 up to 21 m/min of moderate running in treadmill during animal life span exhibited a reversion of all the observed aging effects on intestinal, skeletal, and heart muscles. the introduction of this lifelong exercise protocol prevented the enhancement of lipid peroxidation and sarcopenia and also preserved cellular and ultracellular structures of the ileum This is the first time that the protective effect of a lifelong regular aerobic physical activity against the deleterious effects of aging on intestinal muscle was demonstrated.Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pathol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Physiol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pathol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Morphol, BR-04023062 São Paulo, BrazilWeb of Scienc

Vitamin C and E supplementation prevents mitochondrial damage of ileum myocytes caused by intense and exhaustive exercise training

Rosa EF, Ribeiro RF, Pereira FM, Freymuller E, Aboulafia J, Nouailhetas VL. Vitamin C and E supplementation prevents mitochondrial damage of ileum myocytes caused by intense and exhaustive exercise training. J Appl Physiol 107: 1532-1538, 2009. First published August 20, 2009; doi: 10.1152/japplphysiol.91166.2008.Intense and exhaustive exercise (IEE) is associated with oxidative stress in skeletal muscle, and we recently reported that intestine is sensitive to IEE. in the present study, we investigated the possible relationship between the effects of IEE on morphology and oxidative markers in the ileum and isolated mitochondria. C57BL/6 mice were ascribed either to a control group comprising two subgroups, one sedentary and another exercised for 10 days (E10), or to a corresponding supplemented control group again comprising two subgroups, one sedentary and another exercised for 10 days (E10-V). the IEE program consisted of a single daily treadmill running session at 85% of V(max), until animal exhaustion. Vitamins C (10 mg/kg) and E (10 mg/kg) were concurrently intraperitoneally administered 2 h before the exercise sessions. IEE was shown to cause 1) impairment of ileum internal membrane mitochondria verified by ultramicrography analysis; 2) increase in ileum carbonyl content (117%) and reduction in antioxidant capacity (36%); 3) increase in mitochondria carbonyl content (38%), increase in the percentage of ruptured mitochondria 25.3%), increase in superoxide dismutase activity (186%), and reduction in citrate synthase activity (40.4%) compared with control animals. Observations in the vitamin-supplemented exercised animals (E10-V) were 1) healthy appearance of myocyte mitochondria; 2) decrease in ileum carbonyl content (66%) and increase in antioxidant capacity (53%); 3) decrease in mitochondria carbonyl content (43%), decrease in the percentage of ruptured mitochondria (30%), slight increase in superoxide dismutase activity (7%), and significant increase in citrate synthase activity (121%) compared with E10 animals. Therefore, the present results strongly corroborate the hypothesis that IEE leads to marked disturbances in intestinal mitochondria, mainly in redox status, and affects whole intestinal redox status.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Electron Microscopy, BR-04023062 São Paulo, BrazilCtr Univ Sao Camilo, São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Ctr Electron Microscopy, BR-04023062 São Paulo, BrazilWeb of Scienc

Intestine of dystrophic mice presents enhanced contractile resistance to stretching despite morphological impairment

Protein dystrophin is a component of the dystrophin-associated protein complex, which links the contractile machinery to the plasma membrane and to the extra-cellular matrix. Its absence leads to a condition known as Duchenne muscular dystrophy (DMD), a disease characterized by progressive skeletal muscle degeneration, motor disability, and early death. in mdx mice, the most common DMD animal model, loss of muscle cells is observed, but the overall disease alterations are less intense than in DMD patients. Alterations in gastrointestinal tissues from DMD patients and mdx mice are not yet completely understood. Thus, we investigated the possible relationships between morphological (light and electron microscopy) and contractile function (by recording the isometric contractile response) with alterations in Ca2+ handling in the ileum of mdx mice. We evidenced a 27% reduction in the ileal muscular layer thickness, a partial damage to the mucosal layer, and a partial damage to mitochondria of the intestinal myocytes. Functionally, the ileum from mdx presented an enhanced responsiveness during stretch, a mild impairment in both the electromechanical and pharmacomechanical signaling associated with altered calcium influxinduced contraction, with no alterations in the sarcoplasmic reticulum Ca2+ storage (maintenance of the caffeine and thapsigargin-induced contraction) compared with control animals. Thus, it is evidenced that the protein dystrophin plays an important role in the preservation of both the microstructure and ultrastructure of mice intestine, while exerting a minor but important role concerning the intestinal contractile responsiveness and calcium handling.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Microscopia Eletron, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Biophys, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Ctr Microscopia Eletron, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Escola Paulista Med, Dept Pharmacol, BR-04023062 São Paulo, BrazilFAPESP: 07/58132-9FAPESP: 12/15716-9FAPESP: 07/59976-6Web of Scienc

Reavaliacao dos medidores propostos para a acao da angiotensina II em ileo isolado de cobaia

BV UNIFESP: Teses e dissertaçõe

Desensitization to ANG II in guinea pig ileum depends on membrane repolarization: role of maxi-K+ channel

Desensitization of ANG II tonic contractile response of the guinea pig ileum is related to membrane repolarization determined by Ca2+-activated K+ (maxi-K+) channel opening. ANG II-stimulated depolarized myocytes presented sustained activation of maxi-K+ channels, characterized by reduction from 415 to 12 ms of the closed time constant. ANG II desensitization was prevented by 100 nM iberiotoxin, being reversible within 30 min. Depolarization by KCl, higher than 4 mM, impaired desensitization, suggesting that the membrane potential must attain a threshold to counteract the repolarization induced by maxi-K+ channel opening. Once this value is attained, there is no time dependency because the desensitization process was shut off by addition of KCl along the time course of the tonic response. In contrast, the sustained ACh tonic component was not altered by these maneuvers. We conclude that desensitization of the ANG II tonic component is foremost due to the opening of maxi-K+ channels, leading to membrane repolarization, thus dosing the voltage-dependent Ca2+ channels responsible for the Ca2+ influx that sustains the tonic component in this muscle.Univ Fed Sao Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 Sao Paulo, BrazilUniv Fed Sao Paulo, Dept Biophys, Escola Paulista Med, BR-04023062 Sao Paulo, BrazilWeb of Scienc