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ABSTRACT: The molecular mechanisms that contribute to the pathogenesis of pressure-induced deep tissue injury are largely unknown. This study tested the hypothesis that oxidative stress and DNA damage signalling mechanism in skeletal muscle are involved in deep tissue injury. Adult Sprague Dawley rats were subject to an experimental protocol to induce deep tissue injury. Two compression cycles with a static pressure of 100 mmHg was applied to an area of 1.5 cm(2) over the mid-tibialis region of right limb of the rats. The left uncompressed limb served as intra-animal control. Muscle tissues underneath compression region were collected for examination. Our analyses indicated that pathohistological characteristics including rounding contour of myofibres and extensive nuclei accumulation were apparently shown in compressed muscles. The elevation of 8OHdG immunopositively stained nuclei indicated the presence of oxidative DNA damage. Increase in oxidative stress was revealed by showing significant elevation of 4HNE and decreases in mRNA abundance of SOD1, catalase and GPx, and protein content of SOD2 in compressed muscles relative to control muscles. Increase in nitrosative stress was demonstrated by significant elevation of nitrotyrosine and NOS2 mRNA content. The activation of tumor suppressor p53 signalling was indicated by the remarkable increases in protein contents of total p53 and serine-15 phosphorylated p53. The transcript expression of the DNA-repairing enzyme, Rad23A, was significantly suppressed in compressed muscles. Our time-course study indicated that increased oxidative/nitrosative stress and proapoptotic signalling were maintained in muscles receiving increasing amount of compression cycles and post-compression time. Furthermore, resveratrol was found to attenuate the histological damage, oxidative/nitrosative stress and proapoptotic signalling in response to prolonged moderate compression. In conclusion, our findings are consistent with the hypothesis that oxidative stress and DNA damage signalling in skeletal muscle are involved in the underlying mechanisms responsible for the pathogenesis of pressure-induced deep tissue injury.
Pflügers Archiv - European Journal of Physiology 01/2013; · 4.46 Impact Factor
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ABSTRACT: There are currently no effective therapies for treating pressure-induced deep tissue injury. This study tested the efficacy of pharmacological inhibition of caspase in preventing muscle damage following sustained moderate compression. Adult Sprague-Dawley rats were subjected to prolonged moderate compression. Static pressure of 100 mm Hg compression was applied to an area of 1.5 cm2 in the tibialis region of the right limb of the rats for 6 h each day for two consecutive days. The left uncompressed limb served as intra-animal control. Rats were randomized to receive either vehicle (DMSO) as control treatment (n =8) or 6 mg kg⁻¹ of caspase inhibitor (z-VAD-fmk; n =8) prior to the 6 h compression on the two consecutive days.Muscle tissues directly underneath the compression region of the compressed limb and the same region of control limb were harvested after the compression procedure.Histological examination and biochemical/molecular measurement of apoptosis and autophagy were performed. Caspase inhibition was effective in alleviating the compression-induced pathohistology of muscle. The increases in caspase-3 protease activity, TUNEL index, apoptotic DNA fragmentation and pro-apoptotic factors (Bax, p53 and EndoG) and the decreases in anti-apoptotic factors (XIAP and HSP70) observed in compressed muscle of DMSO-treated animals were not found in animals treated with caspase inhibitor. The mRNA content of autophagic factors (Beclin-1, Atg5 and Atg12) and the protein content of LC3, FoxO3 and phospho-FoxO3 that were down-regulated in compressed muscle of DMSO-treated animals were all maintained at their basal level in the caspase inhibitor treated animals. Our data provide evidence that caspase inhibition attenuates compression-induced muscle apoptosis and maintains the basal autophagy level. These findings demonstrate that pharmacological inhibition of caspase/apoptosis is effective in alleviating muscle damage as induced by prolonged compression.
The Journal of Physiology 05/2011; 589(Pt 13):3349-69. · 4.72 Impact Factor
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ABSTRACT: The molecular mechanism initiating deep pressure ulcer remains to be elucidated. The present study tested the hypothesis that the ubiquitin proteasome system is involved in the signalling mechanism in pressure-induced deep tissue injury.
Adult Sprague Dawley rats were subjected to an experimental compression model to induce deep tissue injury. The tibialis region of the right hind limb was subjected to 100 mmHg of static pressure for six hours on each of two consecutive days. The compression pressure was continuously monitored by a three-axial force transducer within the compression indentor. The left hind limb served as the intra-animal control. Muscle tissues underneath the compressed region were collected and used for analyses.
Our results demonstrated that the activity of 20S proteasome and the protein abundance of ubiquitin and MAFbx/atrogin-1 were elevated in conjunction with pathohistological changes in the compressed muscle, as compared to control muscle. The administration of the proteasome inhibitor MG132 was found to be effective in ameliorating the development of pathological histology in compressed muscle. Furthermore, 20S proteasome activity and protein content of ubiquitin and MAFbx/atrogin-1 showed no apparent increase in the MG132-treated muscle following compression.
Our data suggest that the ubiquitin proteasome system may play a role in the pathogenesis of pressure-induced deep tissue injury.
BMC Musculoskeletal Disorders 03/2011; 12:58. · 1.58 Impact Factor
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ABSTRACT: To examine the immediate effects of 2 vibration protocols with different vibration frequencies that yielded the same maximum acceleration (106.75ms(-2)) on muscle peak torque and stiffness of knee extensor and flexor.
Randomized crossover study with repeated measures.
Laboratory setting.
Recreationally active male adults (N=10).
Participants performed 10 bouts of 60-second static half squats intermitted with a 60-second rest period between bouts on a platform with no vibration (control) and a vibration frequency of 26Hz or 40Hz.
Concentric and eccentric peak torques of knee extensor and flexor were examined within 5 minutes before and after vibration by isokinetic test. Young's modulus as an index of tissue stiffness was determined at quadriceps and hamstring pre- and postvibration by using an ultrasound indentation method.
The 2-way repeated-measures analysis of variance indicated a significant interaction effect between vibration and vibration frequency for knee extensor concentric peak torque (P=.003). The vibration-induced changes of knee extensor concentric peak torque in vibration frequency of 26Hz (14.5Nm) and 40Hz (12.0Nm) were found to be significantly greater than that in controls (-29.4Nm) (P<.05). The change in eccentric peak torque of knee flexor after vibration tended to be greater in 26Hz of vibration frequency when compared with controls (26Hz of vibration frequency vs controls: 13.9±7.1 vs -11.4±5.3Nm, P=.08). No statistically significant differences were obtained in tissue stiffness in the quadriceps and hamstring with any of the conditions.
Our data suggest that whole-body vibration at a frequency of 26Hz and 40Hz preclude the decline in concentric peak torque of knee extensor observed after 10 bouts of 60 seconds of static half squats. A change in muscle mechanical stiffness property as induced by whole-body vibration is not supported by our data.
Archives of physical medicine and rehabilitation 10/2010; 91(10):1608-15. · 2.18 Impact Factor
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ABSTRACT: Pressure ulcer is a complex and significant health problem. Although the factors including pressure, shear, and ischemia have been identified in the etiology of pressure ulcer, the cellular and molecular mechanisms that contribute to the development of pressure ulcer are unclear. This study tested the hypothesis that the early-onset molecular regulation of pressure ulcer involves apoptosis in muscle tissue. Adult Sprague-Dawley rats were subjected to an in vivo protocol to mimic pressure-induced deep tissue injury. Static pressure was applied to the tibialis region of the right limb of the rats for 6 h each day on two consecutive days. The compression force was continuously monitored by a three-axial force transducer equipped in the compression indentor. The contralateral uncompressed limb served as intra-animal control. Tissues underneath the compressed region were collected for histological analysis, terminal dUTP nick-end labeling (TUNEL), cell death ELISA, immunocytochemical staining, and real-time RT-PCR gene expression analysis. The compressed muscle tissue generally demonstrated degenerative characteristics. TUNEL/dystrophin labeling showed a significant increase in the apoptotic muscle-related nuclei, and cell death ELISA demonstrated a threefold elevation of apoptotic DNA fragmentation in the compressed muscle tissue relative to control. Positive immunoreactivities of cleaved caspase-3, Bax, and Bcl-2 were evident in compressed muscle. The mRNA contents of Bax, caspase-3, caspase-8, and caspase-9 were found to be higher in the compressed muscle tissue than control. These results demonstrated that apoptosis is activated in muscle tissue following prolonged moderate compression. The data are consistent with the hypothesis that muscle apoptosis is involved in the underlying mechanism of pressure-induced deep tissue injury.
Journal of Applied Physiology 08/2009; 107(4):1266-75. · 3.75 Impact Factor
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ABSTRACT: Apoptotic signaling proteins were evaluated in postmitotic skeletal myotubes to test the hypothesis that oxidative stress induced by H(2)O(2) activates both caspase-dependent and caspase-independent apoptotic proteins in differentiated C2C12 myotubes. We hypothesized that oxidative stress would decrease anti-apoptotic protein levels in C2C12 myotubes.
Apoptotic regulatory factors and apoptosis-associated proteins including Bcl-2, Bax, Apaf-1, XIAP, ARC, cleaved PARP, p53, p21(Cip1/Waf1), c-Myc, HSP70, CuZnSOD, and MnSOD protein content were measured by immunoblots.
H(2)O(2) induced apoptosis in myotubes as shown by DNA laddering and an elevation of apoptotic DNA fragmentation. Cell death ELISA showed increase in the extent of apoptotic DNA fragmentation following treatment with H(2)O(2). Treatment with 4 mM of H(2)O(2) for 24 or 96 h caused increase in Bax (56%, 227%), cytochrome c (282%, 701%), Smac/DIABLO (155%, 260%), caspase-3 protease activity (51%, 141%), and nuclear and cytosolic p53 (719%, 1581%) levels in the myotubes. As an estimate of the mitochondrial AIF release to the cytosol, AIF protein content measured in the mitochondria-free cytosolic fraction was elevated by 65% after 96 h treatment with 4 mM of H(2)O(2). AIF measured in the nuclear protein fraction increased by 74% and 352% following treatment with 4 mM of H(2)O(2) for 24 and 96 h, respectively. Bcl-2 declined in myotubes by 61% and 69% after 24 or 96 h of treatment in 4 mM H(2)O(2), respectively.
These findings indicate that both caspase-dependent and caspase-independent mechanisms are involved in coordinating the activation of apoptosis induced by H(2)O(2) in differentiated myotubes.
Life sciences 03/2009; 84(13-14):468-81. · 2.56 Impact Factor
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ABSTRACT: Apoptosis is a well-conserved cellular destructive event which has been implicated in a variety of diseases such as cancers and neurodegenerative diseases. The comprehensive investigation of apoptosis has been emerged in the field of skeletal muscle biology. Results have been consistent in demonstrating the activation of apoptotic machinery in different pathologic and physiologic muscle atrophic conditions including muscle disuse, hindlimb unloading, muscle dystrophy, sarcopenia, and neuromuscular diseases. Together with the other identified muscle atrophy-related signaling mechanisms such as NFk B, FOXOs/MuRF1/MAFbx and ubiquitin-proteasome, apoptosis has been advocated as an important candidate in regulating denervation-induced muscle loss. The purpose of this article is to review the role and signaling mechanisms of apoptosis during denervation in skeletal muscle including myofibers and satellite cells.
Frontiers in Bioscience 02/2009; 14:432-52. · 3.52 Impact Factor
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ABSTRACT: Oxidative stress increases during unloading in muscle from young adult rats. The present study examined the markers of oxidative stress and antioxidant enzyme gene and protein expressions in medial gastrocnemius muscles of aged and young adult (30 and 6 mo of age) Fischer 344 x Brown Norway rats after 14 days of hindlimb suspension. Medial gastrocnemius muscle weight was decreased by approximately 30% in young adult and aged rats following suspension. When muscle weight was normalized to animal body weight, it was reduced by 12% and 22% in young adult and aged rats, respectively, after suspension. Comparisons between young adult and aged control animals demonstrated a 25% and 51% decline in muscle mass when expressed as absolute muscle weight and muscle weight normalized to the animal body weight, respectively. H(2)O(2) content was elevated by 43% while Mn superoxide dismutase (MnSOD) protein content was reduced by 28% in suspended muscles compared with control muscles exclusively in the aged animals. Suspended muscles had greater content of malondialdehyde (MDA)/4-hydroxyalkenals (4-HAE) (29% and 58% increase in young adult and aged rats, respectively), nitrotyrosine (76% and 65% increase in young adult and aged rats, respectively), and catalase activity (69% and 43% increase in young adult and aged rats, respectively) relative to control muscles. Changes in oxidative stress markers MDA/4-HAE, H(2)O(2), and MnSOD protein contents in response to hindlimb unloading occurred in an age-dependent manner. These findings are consistent with the hypotheses that oxidative stress has a role in mediating disuse-induced and sarcopenia-associated muscle losses. Our data suggest that aging may predispose skeletal muscle to increased levels of oxidative stress both at rest and during unloading.
Journal of Applied Physiology 10/2008; 105(6):1695-705. · 3.75 Impact Factor
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ABSTRACT: This study examined the effect of ingesting 3 isocaloric meals with different glycemic indices (GI) and glycemic loads (GL) 2 hr before exercise on metabolic responses and endurance running performance. Eight male runners completed 3 trials in a randomized order, separated by at least 7 days. Carbohydrate (CHO) content (%), GI, and GL were, respectively, 65%, 79, and 82 for the high-GI/high-GL meal (H-H); 65%, 40, and 42 for the low-GI/low-GL meal (L-L); and 36%, 78, and 44 for the high-GI/low-GL meal (H-L). Each trial consisted of a 1-hr run at 70% VO2max, followed by a 10-km performance run. Low-GL diets (H-L and L-L) were found to induce smaller metabolic changes during the postprandial period and during exercise, which were characterized by a lower CHO oxidation in the 2 trials (p < .05) and a concomitant, higher glycerol and free-fatty-acid concentration in the H-L trial (p < .05). There was no difference, however, in time to complete the preloaded 10-km performance run between trials. This suggests that the GL of the preexercise meal has an important role in determining subsequent metabolic responses.
International journal of sport nutrition and exercise metabolism 06/2008; 18(3):281-300. · 2.01 Impact Factor
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ABSTRACT: Apoptosis results in DNA fragmentation and, subsequently, destruction of cells containing a single nucleus. Our hypothesis is that multinucleated cells such as muscle fibers can experience apoptotic-induced loss of single nuclei (nuclear apoptosis) without destruction of the entire fiber. The loss of nuclei likely contributes to atrophy and sarcopenia. Furthermore, increased chronic activity attenuates apoptotic signaling, which may reduce sarcopenia.
Exercise and Sport Sciences Reviews 05/2008; 36(2):51-7. · 4.49 Impact Factor
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ABSTRACT: During chronic obstructive pulmonary disease (COPD) diaphragm and peripheral muscle weakness occur. Muscle remodeling and wasting may be a result of apoptosis and changes in muscle-specific transcription factors, such as MyoD, altering muscle-specific gene transcription and muscle regenerative capacity. To investigate this, we instilled under ketamine/xylazine anesthesia porcine elastase in the lungs of hamsters to induce emphysema. The emphysematous hamster is an accepted model for COPD. In the diaphragm and peripheral muscles we assessed the occurrence of apoptosis, and in the diaphragm and soleus also the expression of MyoD and inhibitor of differentiation protein 2 (Id2). There was no significant muscle atrophy in emphysematous hamsters. The mRNA levels of TNF-alpha and markers of apoptosis were significantly elevated in the diaphragm and soleus muscles during emphysema. This was accompanied by an increased presence of nucleosomes in the cytosol. Caspase 3 activity and the DNA-binding activity of the p65 subunit of NF-kappaB, however, were unaltered in all muscles. The protein expression of MyoD and Id2 were decreased and increased in the diaphragm and the soleus muscle, respectively. Thus, despite the absence of muscle atrophy in emphysematous hamsters, there was evidence of increased TNF-alpha expression, apoptosis, and altered muscle-specific transcriptional regulation as reflected by decreased MyoD and elevated Id2 levels at least in the soleus and diaphragm muscle. These alterations may impair the regenerative capacity of skeletal muscles and ultimately contribute to muscle wasting.
AJP Regulatory Integrative and Comparative Physiology 07/2007; 293(1):R135-44. · 3.34 Impact Factor
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ABSTRACT: Interleukin-15 (IL-15) mRNA is constitutively expressed in skeletal muscle. Although IL-15 has proposed hypertrophic and anti-apoptotic roles in vitro, its role in skeletal muscle cells in vivo is less clear. The purpose of this study was to determine if skeletal muscle aging and unloading, two conditions known to promote muscle atrophy, would alter basal IL-15 expression in skeletal muscle. We hypothesized that IL-15 mRNA expression would increase as a result of both aging and muscle unloading and that muscle would express the mRNA for a functional trimeric IL-15 receptor (IL-15R). Two models of unloading were used in this study: hindlimb suspension (HS) in rats and wing unloading in quail. The absolute muscle wet weight of plantaris and soleus muscles from aged rats was significantly less when compared with muscles from young adult rats. Although 14 days of HS resulted in reduced muscle mass of plantaris and soleus muscles from young adult animals, this effect was not observed in muscles from aged animals. A significant aging times unloading interaction was observed for IL-15 mRNA in both rat soleus and plantaris muscles. Patagialis (PAT) muscles from aged quail retained a significant 12 and 6% of stretch-induced hypertrophy after 7 and 14 days of unloading, respectively. PAT muscles from young quail retained 15% hypertrophy at 7 days of unloading but regressed to control levels following 14 days of unloading. A main effect of age was observed on IL-15 mRNA expression in PAT muscles at 14 days of overload, 7 days of unloading, and 14 days of unloading. Skeletal muscle also expressed the mRNAs for a functional IL-15R composed of IL-15Ralpha, IL-2/15R-beta, and -gammac. Based on these data, we speculate that increases in IL-15 mRNA in response to atrophic stimuli may be an attempt to counteract muscle mass loss in skeletal muscles of old animals. Additional research is warranted to determine the importance of the IL-15/IL-15R system to counter muscle wasting.
AJP Cell Physiology 05/2007; 292(4):C1298-304. · 3.54 Impact Factor
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ABSTRACT: This study tested the hypothesis that aging exacerbates apoptotic signaling in rat fast plantaris muscle during muscle unloading. Plantaris muscle mass was 22% lower in aged animals and the apoptotic index was 600% higher, when compared to those in young adult animals. Following 14 days of hind-limb unloading, absolute plantaris muscle mass was 20% lower in young adult animals with a corresponding 200% higher elevation of the apoptotic index. Unloading had no affect on muscle weight or apoptotic index of aged plantaris muscles. The changes in pro-apoptotic messenger RNA (mRNA) for apoptotic protease activating factor-1 (Apaf-1), Bax, and inhibitor of differentiation protein-2 (Id2) were exacerbated with aging. Bax and Bcl-2 protein levels were also altered differently in aged muscle, compared to young. Significant positive correlations were observed between the changes in Id2 and Bax mRNA, and Id2 and caspase-9 mRNA. These data suggest that a pro-apoptotic environment may contribute to aging-associated atrophy in fast skeletal muscle, but apoptotic signaling differs by age.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 04/2006; 61(3):245-55. · 4.60 Impact Factor
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ABSTRACT: This study tested the hypothesis that inhibitor of differentiation-2 (Id2), p53, and heat shock proteins (HSP) are responsive to suspension-induced muscle atrophy. Fourteen days of hindlimb suspension were used to unload the hindlimbs and induce atrophy in gastrocnemius muscles of young adult and aged rats. Following suspension, medial gastrocnemius muscle wet weight was reduced by approximately 30%, and the muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively. mRNA abundances of Id2, p53, HSP70-2, and HSP27 did not change with suspension, whereas HSP70-1 mRNA content was lower in the suspended muscle compared with the control muscle in both young adult and aged animals. Our immunoblot analyses indicated that protein expressions of HSP70 and HSP60 were not different between suspended and control muscles in both ages, whereas HSP27 protein content was increased in suspended muscle relative to control muscle only in young adult animals. Id2 and p53 protein contents were elevated in the cytosolic fraction of suspended muscle compared with the control muscle in both young and aged animals, but these changes were not found in the nuclear protein fraction. Furthermore, compared with young adult, aged muscles had a lower HSP70-1 mRNA content but higher HSP70-2 mRNA content and protein contents of Id2, p53, HSP70, and HSP27. These findings are consistent with the hypothesis that Id2 and p53 are responsive to unloading-induced muscle atrophy. Moreover, our data indicate that aging is accompanied with altered abundances of HSP70-1 and HSP70-2 mRNA, in addition to Id2, p53, HSP70, and HSP27 protein in rat gastrocnemius muscle.
Journal of Applied Physiology 04/2006; 100(3):907-16. · 3.75 Impact Factor
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ABSTRACT: This study tested the hypothesis that loading decreased apoptosis in skeletal muscle in an aging-dependent fashion. One wing of young and aged Japanese quails was loaded for 7 or 21 days to induce hypertrophy. The contralateral wing served as the intra-animal control. Loading increased fast-twitch quail patagialis muscle mass by 28 and 49%, after 7 or 21 days of loading, respectively in young adult birds. Muscle mass was not elevated after 7 days of loading, but increased by 29% after 21 days of loading in aged birds. Seven days of loading reduced DNA fragmentation and cytosolic accumulation of cytochrome c in muscles from young birds but not in muscles from aged birds. ARC protein content was lower and H2O2 content was higher in muscles from aged birds following 7 days of loading. The mitochondria-free cytosolic protein fraction from muscles loaded for 7 days had 41 and 29% lower AIF content than control muscles in young and aged birds, respectively. XIAP, an apoptotic suppressor protein increased after 7 days of loading in muscles from young adult but not aged birds. Our results suggest that loading suppresses pro-apoptotic signaling in quail muscle but aging delays or attenuates these anti-apoptotic changes.
Experimental Gerontology 03/2006; 41(2):175-88. · 3.74 Impact Factor
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ABSTRACT: Tumor suppressor p53 and inhibitor of DNA-binding/differentiation Id2 were examined after 7 or 21 days of wing weighting in fast patagialis (PAT) and slow anterior latissimus dorsi (ALD) wing muscles of young adult and old Japanese quails. The contralateral wing served as the intra-animal control. Seven days of loading increased PAT and ALD muscle weight by 28 and 96%, respectively, in young birds. PAT and ALD muscle weight was 49 and 179% greater, respectively, than control muscles after 21 days of loading in young birds. In aged birds, no PAT or ALD hypertrophy was found after 7 days of loading; however, PAT and ALD muscle weight increased by 29 and 102%, respectively, after 21 days of loading. Id2 protein in the nuclear muscle fraction increased in both PAT and ALD muscles from young adult and old birds that were loaded for 7 days and in ALD muscles after 21 days of loading relative to contralateral control muscles. Nuclear p53 protein was greater in 7- or 21-day loaded PAT and ALD muscles relative to control muscles in both age groups. Cytosolic Id2 and p53 protein contents were not changed in loaded PAT or ALD muscles relative to control muscles at any time point. These data suggest that nuclear, but not cytosolic, Id2 and p53 are responsive to stretch-induced muscle overload. Moreover, the attenuated ability of the aged skeletal muscle to achieve hypertrophy does not appear to be explained by the subcellular changes in Id2 and p53 content with overload.
Journal of Applied Physiology 12/2005; 99(5):1897-904. · 3.75 Impact Factor
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ABSTRACT: In the present study, we examined the responses of apoptosis and apoptotic regulatory factors to muscle hypertrophy induced by stretch overload in quail slow-tonic muscles. The wings from one side of young and aged Japanese quails were loaded by attaching a tube weight corresponding to 12% of the bird's body weight for 7 or 21 days. Muscle from the contralateral side served as the intraanimal control. Relative to the intraanimal contralateral control side, the muscle wet weight increased by 96% in young birds, whereas the muscle weight gain in aged birds was not significant after 7 days of loading. After 21 days of loading, muscle weight significantly increased by 179% and 102% in young and aged birds, respectively. Heat shock protein (HSP)72 and HSP27 protein contents in the loaded sides were higher than on the control sides exclusively in young birds after 7 days of loading. Compared with the contralateral control muscle, the extent of apoptotic DNA fragmentation and the total cytosolic apoptosis-inducing factor protein content were reduced in all loaded muscles except for the 7-day-loaded muscles from the aged birds. Bax protein content was diminished in the loaded muscle relative to the control side from all groups, whereas Bcl-2 protein content was reduced in the young and aged muscles after 21 days of loading. The total cytosolic cytochrome c protein content was decreased and the X chromosome-linked inhibitor of apoptosis protein content was elevated in 7- and 21-day-loaded muscles relative to the intraanimal control muscle from young birds. Furthermore, after 7 days of loading the muscles of aged birds, H(2)O(2) content and the total cytosolic protein content of second mitochondrial activator of caspases/direct inhibitor of apoptosis-binding protein with low isoelectric point were elevated compared with the intraanimal control side. These data suggest that stretch overload-induced muscle hypertrophy is associated with changes in apoptosis in slow-tonic skeletal muscle. Moreover, discrepant apoptotic responses to muscle overload in young and aged muscles may account in part for the age-related decline in the capability for muscle hypertrophy.
AJP Cell Physiology 12/2005; 289(5):C1105-13. · 3.54 Impact Factor
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ABSTRACT: Although apoptosis has been demonstrated in soleus during hindlimb suspension (HS), it is not known whether apoptosis is also involved in the loss of muscles dominated by mixed fibers. Therefore, we examined the apoptotic responses in gastrocnemius muscles of young adult and aged Fischer 344 x Brown Norway rats after 14 days of HS. The medial gastrocnemius muscle wet weight significantly decreased by 30 and 32%, and muscle wet weight normalized to the animal body weight decreased by 11 and 15% in young adult and aged animals, respectively, after HS. The extent of apoptotic DNA fragmentation increased by 119 and 61% in suspended muscles from young and aged rats, respectively. Bax mRNA increased by 73% in young muscles after HS. Bax and Bcl-2 protein levels were greater in suspended muscles relative to control muscles in both age groups. The level of cytosolic mitochondria-housed apoptotic factor cytochrome c was significantly increased in the mitochondria-free cytosol of suspended muscles from young and aged rats. In contrast, the release/accumulation of AIF, a caspase-independent apoptogenic factor, was exclusively expressed in the suspended muscles from aged rats. Our data also show that aging favors the proapoptotic signaling in skeletal muscle by altering the contents of Bax, Bcl-2, Apaf-1, AIF, caspases, XIAP, Smac/DIABLO, and cytochrome c. Furthermore, these results indicate that apoptosis occurs not only in slow-twitch soleus muscle but also in the mixed-fiber (predominately fast fibered) gastrocnemius muscle. Our data are consistent with the hypothesis that apoptotic signaling differs in young adult and aged gastrocnemius muscles during HS.
AJP Regulatory Integrative and Comparative Physiology 11/2005; 289(4):R1015-26. · 3.34 Impact Factor
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ABSTRACT: Muscle hypertrophy is an adaptive response to overload that requires increasing gene transcription and synthesis of muscle-specific proteins resulting in increased protein accumulation. Progressive resistance training (P(RT)) is thought to be among the best means for achieving hypertrophy in humans. However, hypertrophy and functional adaptations to P(RT) in the muscles of humans are often difficult to evaluate because adaptations can take weeks, months, or even years before they become evident, and there is a large variability in response to P(RT) among humans. In contrast, various animal models have been developed which quickly result in extensive muscle hypertrophy. Several such models allow precise control of the loading parameters and records of muscle activation and performance throughout overload. Scientists using animal models of muscle hypertrophy should be familiar with the advantages and disadvantages of each and thereby choose the model that best addresses their research question. The purposes of this paper are to review animal models currently being used in basic research laboratories, discuss the hypertrophic and functional outcomes as well as applications of these models to aging, and highlight a few mechanisms involved in regulating hypertrophy as a result of applying these animal models to questions in research on aging.
Canadian journal of applied physiology = Revue canadienne de physiologie appliquée 11/2005; 30(5):591-624. · 1.30 Impact Factor
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ABSTRACT: This study tested the hypotheses that apoptotic suppressors: (a) increase during muscle overload, (b) decrease in response to unloading following hypertrophy, and (c) respond to unloading in an aging-dependent fashion. Following 14 days of stretch-induced overloading, the X-linked inhibitor of apoptosis protein (XIAP) was elevated by 140% and 116% in patagialis (PAT) muscles of young and old quail, respectively, when compared to the contralateral control side. XIAP messenger RNA (mRNA) or protein was not different in experimental and control muscles of young birds after 7 or 14 days of unloading. In old birds, PAT XIAP mRNA and protein were 47% and 67% greater in experimental than in control muscles, respectively, after 7 days of unloading. Furthermore, XIAP mRNA had returned to control level by 14 days of unloading, but XIAP protein content was 57% greater than control muscles after 14 days of unloading. Higher levels of XIAP during unloading in old than in young muscles may be an attempt to counterbalance apoptosis-induced muscle atrophy.
The Journals of Gerontology Series A Biological Sciences and Medical Sciences 09/2005; 60(8):976-83. · 4.60 Impact Factor
