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The 20S proteasome β-subunit immunoblot percentage of change in expression between baseline and peak training, based on densitometry results for each dog.

The 20S proteasome β-subunit immunoblot percentage of change in expression between baseline and peak training, based on densitometry results for each dog.

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The effects of long-term athletic training are associated with excessive skeletal muscle turnover attributable to increased rates of myofibrillar protein synthesis and proteolysis, which are mechanisms poorly understood in the athletic dog. A physiologic field study using 44 English pointers and Labrador retrievers that had been purposely bred for...

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... was no significant change in the regu- lation of the β-subunit of the 20S proteasome catalytic core based on densitometric evalua- tion of Western blots when baseline and peak- training results were compared. The average percentage change in the densitometric read- ings between pretraining and peak training was 10.6% ± 49.6% (Figure 1). The p31 expres- sion, as an indication of regulatory capping expression, showed a moderate degree of exercise-induced up-regulation (48% ± 69%; P < .001) ...

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... Results from Post-0 of this study showed that exercise did not The CAPN-2 expression increases after exercise aligns with Belcastro (Belcastro 1993). CAPN-2 was significantly downregulated 24 h after exercise compared to Post-0 in Groups S and M, which could be induced by upregulated ubiquitin-proteasome pathway (Wakshlag et al. 2002). CAPN-2 expression increased in Groups E and M compared to Group C 48 h after exercise, which could be the result of an inflammatory response to protein degradation (Raj et al. 1998). ...
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The purpose of this study was to compare the effects of two different originated peptide, namely, marine collagen peptide (MCP) and soy peptide (SP) on Calpain-1 (CAPN-1) and Calpain-2 (CAPN-2) and skeletal muscle micro-injury. Method: One hundred male SD rats were divided into four groups: control group (Group C, n = 10), exercise + MCP group (Group M, n = 30), exercise + SP group (Group S, n = 30), and exercise group (Group E, n = 30). After six weeks of training, blood and skeletal muscle were taken immediately, 24 h, and 48 h after exercise. IGF-1, CK, testosterone (T), and skeletal muscle expression of CAPN-1 and CAPN-2 were tested. Results: IGF-1 of Group S was greater immediately after exercise compared to Group E (p <0.05), and T recovery was faster in Group M than E (p <0.05). CK was upregulated in Groups E and M immediately after exercise, while Group S had greater CK than Groups E and C (p <0.05). Group M had higher CAPN-1 expression in quadriceps than Groups E and S (p <0.05) immediately after exercise. CAPN-2 expression in gastrocnemius was upregulated immediately after exercise. T was negatively correlated with CAPN-2 expression in quadriceps (r = -0.715, p <0.05) immediately after exercise, and it was negatively correlated with CAPN-1 expression in gastrocnemius (r = -0.905, p <0.05) 24 h after exercise. Conclusion: Both peptides demonstrated limited effect on post-exercise CK, CAPN-1, and CAPN-2. Compared with SP, MCP had a more significant effect on recovery of T after exercise. And SP was more effective than MCP in downregulating exercise-induced upregulation of CAPN-1 and CAPN-2 expression observed 48 h after exercise in gastrocnemius.
... The degradation of cellular proteins mediated by the ubiquitin-26S proteasome pathway is a complex and rigorous process in eukaryotic cells. This highly selective protein degradation pathway plays an important role in the regulation of cell cycle progression [11], apoptosis [12], metabolic regulation [13], signal transduction [14] and so on. As far as current knowledge is concerned, 26S proteasome is a multiplesubunit protein complex composed of the 20S degradation complex (CP) and the 19S regulatory complex (RP) [15]. ...
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Cholangiocarcinoma (CCA) has been well known as the second most common primary tumor of hepatobiliary system. PSMC2 (proteasome 26S subunit ATPase 2) is a key member of the 19S regulatory subunit of 26S proteasome, responsible for catalyzing the unfolding and translocation of substrates into the 20S proteasome, whose role in CCA is totally unknown. In this study, the results of immunohistochemistry analysis showed the upregulation of PSMC2 in CCA tissues compared with normal tissues, which was statistically analyzed to be associated with CCA tumor grade. Subsequently, the loss-of-function study suggested that knockdown of PSMC2 significantly suppressed cell proliferation, cell migration, promoted cell apoptosis and arrested cell cycle distribution in vitro. The decreased tumorigenicity of CCA cells with PSMC2 knockdown was confirmed in vivo by using mice xenograft model. In PSMC2 knockdown cells, pro-apoptotic protein Caspase3 was upregulated; anti-apoptotic proteins such as Bcl-2 and IGF-II were downregulated; among EMT markers, E-cadherin was upregulated while N-cadherin and Vimentin were downregulated, by which may PSMC2 regulates cell apoptosis and migration. Furthermore, through RNA-seq and verification by qPCR, western blotting and co-IP assays, CDK1 was identified as the potential downstream of PSMC2 mediated regulation of CCA. PSMC2 and CDK1 showed mutual regulation effects on expression level of each other. Knockdown of PSMC2 could aggregate the influence of CDK1 knockdown on cellular functions of CCA cells. In summary, our findings suggested that PSMC2 possesses oncogene-like functions in the development and progression of CCA through regulating CDK1, which may be used as an effective therapeutic target in CCA treatment.
... Previous studies have showed that 26S proteasome participated in the regulation of a variety of biological processes such as cell cycle progression [15], apoptosis [16], metabolic regulation [17], and signal transduction [18]. With the continuous exploration of 26S proteasome, its substrates have attracted considerable attention. ...
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Background Prostate cancer is the most common malignant tumor of male genitourinary system, molecular mechanism of which is still not clear. PSMC2 (proteasome 26S subunit ATPase 2) is a key member of the 19S regulatory subunit of 26S proteasome, whose relationship with prostate cancer is rarely studied. Methods Here, expression of PSMC2 in tumor tissues or cells of prostate cancer was detected by qPCR, western blotting and immunohistochemical analysis. The effects of PSMC2 knockdown on cell proliferation, colony formation, cell migration, cell cycle and apoptosis were assessed by Celigo cell counting assay, colony formation assay, wound-healing assay, Transwell assay and flow cytometry, respectively. The influence of PSMC2 knockdown on tumor growth in vivo was evaluated by mice xenograft models. Results The results demonstrated that PSMC2 was upregulated in tumor tissues of prostate cancer and its high expression was significantly associated with advanced Gleason grade and higher Gleason score. Knockdown of PSMC2 could inhibited cell proliferation, colony formation and cell migration of prostate cancer cells, while promoting cell apoptosis and cell cycle arrest. The suppression of tumor growth in vivo by PSMC2 knockdown was also showed by using mice xenograft models. Moreover, the regulation of prostate cancer by PSMC2 may be mediated by Akt/Cyclin D1/CDK6 signaling pathway. Conclusions Therefore, our studies suggested that PSMC2 may act as a tumor promotor in the development and progression of prostate cancer, and could be considered as a novel therapeutic target for prostate cancer treatment.
... Accordingly, RT has previously been shown to increase the mRNA level of proteasome 20S α-1 subunit (Psma1) and ubiquitin B (Ubb), genes implicated in the UPP [37], while ET increases 26S proteasome activity in healthy mice [18]. Additionally, an increase in molecular markers of UPP activity has been observed following long-term training in hunting dogs [65]. The increase post-RT in atrogin-1 mRNA is consistent with previous observations following 8 weeks [37], but not 21 weeks [28], of hypertrophy-inducing RT. ...
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Knowledge on the effects of divergent exercise on ostensibly protein degradation pathways may be valuable for counteracting muscle wasting and for understanding muscle remodelling. This study examined mRNA and/or protein levels of molecular markers of the ubiquitin proteasome pathway (UPP), including FBXO32 (atrogin-1), MURF-1, FBXO40, FOXO1 and FOXO3. Protein substrates of atrogin-1-including EIF3F, MYOG and MYOD1-and of MURF-1-including PKM and MHC-were also measured. Subjects completed 10 weeks of endurance training (ET) or resistance training (RT) followed by a single-bout of endurance exercise (EE) or resistance exercise (RE). Following training, atrogin-1, FBXO40, FOXO1 and FOXO3 mRNA increased independently of exercise mode, whereas MURF-1 mRNA and FOXO3 protein increased following ET only. No change in other target proteins occurred post-training. In the trained state, single-bout EE, but not RE, increased atrogin-1, MURF-1, FBXO40, FOXO1, FOXO3 mRNA and FOXO3 protein. In contrast to EE, FBXO40 mRNA and protein decreased following single-bout RE. MURF-1 and FOXO1 protein levels as well as the protein substrates of atrogin-1 and MURF-1 were unchanged following training and single-bout exercise. This study demonstrates that the intracellular signals elicited by ET and RT result in an upregulation of UPP molecular markers, with a greater increase following ET. However, in the trained state, the expression levels of UPP molecular markers are increased following single-bout EE, but are less responsive to single-bout RE. This suggests that adaptations following endurance exercise training are more reliant on protein UPP degradation processes than adaptations following resistance exercise training.
... This amount of protein is lower than the Association of American Feed Control Officials (AAFCO) standards, but above the NRC requirements for protein, suggesting that lowprotein diets may not be detrimental to all athletic endeavors; however, long-term feeding of low-protein diets and their overall effect on performance has not been evaluated. [39][40][41][42][43] Therefore, 24% ME protein (60 g/1000 kcal) is likely a reasonably adequate intake for sprinters and intermediate athletes not participating in long-duration endurance activities. Endurance athletes may require more dietary protein (closer to 30% ME or higher); however, definitive studies to elucidate the ideal amounts of protein in endurance athletes have yet to be performed. ...
Article
Conformation, genetics, and behavioral drive are the major determinants of success in canine athletes, although controllable variables, such as training and nutrition, play an important role. The scope and breadth of canine athletic events has expanded dramatically in the past 30 years, but with limited research on performance nutrition. There are considerable data examining nutritional physiology in endurance dogs and in sprinting dogs; however, nutritional studies for agility, field trial, and detection are rare. This article highlights basic nutritional physiology and interventions for exercise, and reviews newer investigations regarding aging working and service dogs, and canine detection activities.
... Aerobic exercise training upregulates skeletal muscle calpain and ubiquitin-proteasome systems in healthy mice proteolysis; cross-sectional area; calpastatin; skeletal muscle plasticity OVER THE LAST DECADES, THE contribution of proteolytic pathways to skeletal muscle plasticity upon different stimuli has been widely investigated (13,14,24). Skeletal muscle calpains and the ubiquitin-proteasome system (UPS) are major intracellular proteolytic systems known to be affected by exercise (28,30,32,39,42,43). The UPS is responsible for most of intracellular protein degradation (Ͼ80%), including sarcomeric proteins (7,20); however, the proteasome could not degrade intact myofibrillar proteins until they are disassembled and removed from the myofibril (36). ...
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Aerobic exercise training (AET) is an important mechanical stimulus that modulates skeletal muscle protein turnover, leading to structural rearrangement. Since the ubiquitin-proteasome system (UPS) and calpain system are major proteolytic pathways involved in protein turnover, we aimed to investigate the effects of intensity-controlled AET on the skeletal muscle UPS and calpain system and their association to training-induced structural adaptations. Long-lasting effects of AET were studied in C57BL/6J mice after 2 or 8 wk of AET. Plantaris cross-sectional area (CSA) and capillarization were assessed by myosin ATPase staining. mRNA and protein expression levels of main components of the UPS and calpain system were evaluated in plantaris by real-time PCR and Western immunoblotting, respectively. No proteolytic system activation was observed after 2 wk of AET. Eight weeks of AET resulted in improved running capacity, plantaris capillarization, and CSA. Muscle RING finger-1 mRNA expression was increased in 8-wk-trained mice. Accordingly, elevated 26S proteasome activity was observed in the 8-wk-trained group, without accumulation of ubiquitinated or carbonylated proteins. In addition, calpain abundance was increased by 8 wk of AET, whereas no difference was observed in its endogenous inhibitor calpastatin. Taken together, our findings indicate that skeletal muscle enhancements, as evidenced by increased running capacity, plantaris capillarization, and CSA, occurred in spite of the upregulated UPS and calpain system, suggesting that overactivation of skeletal muscle proteolytic systems is not restricted to atrophying states. Our data provide evidence for the contribution of the UPS and calpain system to metabolic turnover of myofibrillar proteins and skeletal muscle adaptations to AET.
... These differences in muscle fiber atrophy can be due to differences in the type of muscle lesion caused by the CMV and the PSV modes. In fact, like peripheral skeletal muscle models, during PSV, diaphragm undergoes a type of exercise in which there is an increase in respiratory activity (in comparison to the CMV) [45][46][47] . This exercise could protect diaphragm from modifications related to muscular inactivity caused by CMV. ...
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The objective of this study was to analyze the effects of Pressure Controlled Ventilation mode (PCV-C) and PSV mode in diaphragm muscle of rats. Wistar rats (n=18) were randomly assigned to the control group or to receive 6 hours of PCV and PSV. After this period, animals were euthanized and their diaphragms were excised, frozen in liquid nitrogen and stored in at -80º C for further histomorphometric analysis. Results showed a 15% decrease in cross-sectional area of muscle fibers on the PCV-C group when compared to the control group (p<0.001) and by 10% when compared to the PSV group (p<0.05). Minor diameter was decreased in PCV-C group by 9% when compared with the control group (p<0.001) and by 6% when compared to the PSV group (p<0.05). When myonuclear area was analyzed, a 16% decrease was observed in the PCV-C group when compared to the PSV group (p<0.05). No significant difference between the groups was observed in myonuclear perimeter (p>0.05). Short-term controlled mechanical ventilation seems to lead to muscular atrophy in diaphragm fibers. The PSV mode may attenuate the effects of VIDD.
... Though the effects of regular physical activity on the total radical trapping antioxidant potential (TRAP), catalase (CAT) activity and glutathione peroxidase (GPX) activity have been inconsistent and controversial, in particular Sharpe and others have illustrated that regular physical activity cannot directly increase the TRAP in serum as index by the concentrations of urate, protein thiols, ascorbate, alpha tocopherol and bilirubin [41], the superoxide dismutase (SOD) activity has consistently been shown to increase with physical activity in an intensity-dependent manner [42]. In addition, ample evidences have indicated that regular physical activity can increase the activity of proteasome complex, which increase the degradation and turnover rate of oxidative modified proteins [43,44]. ...
Article
Despite great progress made in sports medicine, the physiological mechanism of moderate physical activity-induced physical fitness remains only partly understood. Combined with the hormetic characteristic of physical activity and property of allostasis, we first propose the hormesis induced allostatic buffering capacity enhancement as a physiological mechanism to explain the moderate physical activity-induced physical fitness. As stressful stimulus, physical activity can induce several stresses in the host, including eustress ('good stress') and distress ('bad stress'), which may have both positive and negative effects. Too little or too much physical activities will introduce too weak eustress or too strong distress and result in allostasis load through weakening allostatic buffering capacity or damaging allostatic buffering capacity respectively. However, moderate physical activities will introduce eustress and contribute to the hormesis induced allostatic buffering capacity enhancement, which benefits organism.
... These differences in modification of metabolism may be due to differences in the type of diaphragmatic muscle damage caused by CMV and PSV. Indeed, as for peripheral skeletal muscle models, during PSV the diaphragm is subjected to exercise type activity through an increase in respiratory activity (versus CMV) [42][43][44]. This exercise would protect the diaphragm from modifications related to muscular inactivity caused by CMV. ...
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Controlled mechanical ventilation (CMV) induces profound modifications of diaphragm protein metabolism, including muscle atrophy and severe ventilator-induced diaphragmatic dysfunction. Diaphragmatic modifications could be decreased by spontaneous breathing. We hypothesized that mechanical ventilation in pressure support ventilation (PSV), which preserves diaphragm muscle activity, would limit diaphragmatic protein catabolism. Forty-two adult Sprague-Dawley rats were included in this prospective randomized animal study. After intraperitoneal anesthesia, animals were randomly assigned to the control group or to receive 6 or 18 hours of CMV or PSV. After sacrifice and incubation with 14C-phenylalanine, in vitro proteolysis and protein synthesis were measured on the costal region of the diaphragm. We also measured myofibrillar protein carbonyl levels and the activity of 20S proteasome and tripeptidylpeptidase II. Compared with control animals, diaphragmatic protein catabolism was significantly increased after 18 hours of CMV (33%, P = 0.0001) but not after 6 hours. CMV also decreased protein synthesis by 50% (P = 0.0012) after 6 hours and by 65% (P < 0.0001) after 18 hours of mechanical ventilation. Both 20S proteasome activity levels were increased by CMV. Compared with CMV, 6 and 18 hours of PSV showed no significant increase in proteolysis. PSV did not significantly increase protein synthesis versus controls. Both CMV and PSV increased protein carbonyl levels after 18 hours of mechanical ventilation from +63% (P < 0.001) and +82% (P < 0.0005), respectively. PSV is efficient at reducing mechanical ventilation-induced proteolysis and inhibition of protein synthesis without modifications in the level of oxidative injury compared with continuous mechanical ventilation. PSV could be an interesting alternative to limit ventilator-induced diaphragmatic dysfunction.
... In support of this possibility we also observed an increase in Psam1 and UBB mRNA, which encode proteins implicated in the ubiquitin proteosome pathway (UPP). Similar to our observation, previous studies in working field dogs have demonstrated an up-regulation of specific components of the UPP at the end of the hunting season (Wakshlag et al. 2002). Combined, these results indicate an important role in the proteolytic process associated with skeletal muscle turnover during long-term training. ...
Article
Skeletal muscle size is tightly regulated by the synergy between anabolic and catabolic signalling pathways which, in humans, have not been well characterized. Akt has been suggested to play a pivotal role in the regulation of skeletal muscle hypertrophy and atrophy in rodents and cells. Here we measured the amount of phospho-Akt and several of its downstream anabolic targets (glycogen synthase kinase-3beta (GSK-3beta), mTOR, p70(s6k) and 4E-BP1) and catabolic targets (Foxo1, Foxo3, atrogin-1 and MuRF1). All measurements were performed in human quadriceps muscle biopsies taken after 8 weeks of both hypertrophy-stimulating resistance training and atrophy-stimulating de-training. Following resistance training a muscle hypertrophy ( approximately 10%) and an increase in phospho-Akt, phospho-GSK-3beta and phospho-mTOR protein content were observed. This was paralleled by a decrease in Foxo1 nuclear protein content. Following the de-training period a muscle atrophy (5%), relative to the post-training muscle size, a decrease in phospho-Akt and GSK-3beta and an increase in Foxo1 were observed. Atrogin-1 and MuRF1 increased after the hypertrophy and decreased after the atrophy phases. We demonstrate, for the first time in human skeletal muscle, that the regulation of Akt and its downstream signalling pathways GSK-3beta, mTOR and Foxo1 are associated with both the skeletal muscle hypertrophy and atrophy processes.