Browsing by Author "Curi R"
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- ItemAutophagy signaling in hypertrophied muscles of diabetic and control rats.(John Wiley and Sons Ltd on behalf of Federation of European Biochemical Societies., 2023-07-20) Scervino MVM; Fortes MAS; Vitzel KF; de Souza DR; Murata GM; Santana GO; da Silva EB; Levada-Pires AC; Kuwabara WMT; Loureiro TCA; Curi R; Krützfeldt JAutophagy plays a vital role in cell homeostasis by eliminating nonfunctional components and promoting cell survival. Here, we examined the levels of autophagy signaling proteins after 7 days of overload hypertrophy in the extensor digitorum longus (EDL) and soleus muscles of control and diabetic rats. We compared control and 3-day streptozotocin-induced diabetic rats, an experimental model for type 1 diabetes mellitus (T1DM). EDL muscles showed increased levels of basal autophagy signaling proteins. The diabetic state did not affect the extent of overload-induced hypertrophy or the levels of autophagy signaling proteins (p-ULK1, Beclin-1, Atg5, Atg12-5, Atg7, Atg3, LC3-I and II, and p62) in either muscle. The p-ULK-1, Beclin-1, and p62 protein expression levels were higher in the EDL muscle than in the soleus before the hypertrophic stimulus. On the contrary, the soleus muscle exhibited increased autophagic signaling after overload-induced hypertrophy, with increases in Beclin-1, Atg5, Atg12-5, Atg7, Atg3, and LC3-I expression in the control and diabetic groups, in addition to p-ULK-1 in the control groups. After hypertrophy, Beclin-1 and Atg5 levels increased in the EDL muscle of both groups, while p-ULK1 and LC3-I increased in the control group. In conclusion, the baseline EDL muscle exhibited higher autophagy than the soleus muscle. Although TDM1 promotes skeletal muscle mass loss and strength reduction, it did not significantly alter the extent of overload-induced hypertrophy and autophagy signaling proteins in EDL and soleus muscles, with the two groups exhibiting different patterns of autophagy activation.
- ItemChanges in Skeletal Muscle Protein Metabolism Signaling Induced by Glutamine Supplementation and Exercise.(MDPI (Basel, Switzerland), 2023-11-07) Rodrigues Junior CF; Murata GM; Gerlinger-Romero F; Nachbar RT; Marzuca-Nassr GN; Gorjão R; Vitzel KF; Hirabara SM; Pithon-Curi TC; Curi R; Lemon PWRAIM: To evaluate the effects of resistance exercise training (RET) and/or glutamine supplementation (GS) on signaling protein synthesis in adult rat skeletal muscles. METHODS: The following groups were studied: (1) control, no exercise (C); (2) exercise, hypertrophy resistance exercise training protocol (T); (3) no exercise, supplemented with glutamine (G); and (4) exercise and supplemented with glutamine (GT). The rats performed hypertrophic training, climbing a vertical ladder with a height of 1.1 m at an 80° incline relative to the horizontal with extra weights tied to their tails. The RET was performed three days a week for five weeks. Each training session consisted of six ladder climbs. The extra weight load was progressively increased for each animal during each training session. The G groups received daily L-glutamine by gavage (one g per kilogram of body weight per day) for five weeks. The C group received the same volume of water during the same period. The rats were euthanized, and the extensor digitorum longus (EDL) muscles from both hind limbs were removed and immediately weighed. Glutamine and glutamate concentrations were measured, and histological, signaling protein contents, and mRNA expression analyses were performed. RESULTS: Supplementation with free L-glutamine increased the glutamine concentration in the EDL muscle in the C group. The glutamate concentration was augmented in the EDL muscles from T rats. The EDL muscle mass did not change, but a significant rise was reported in the cross-sectional area (CSA) of the fibers in the three experimental groups. The levels of the phosphorylated proteins (pAkt/Akt, pp70S6K/p70S6K, p4E-BP1/4E-BP1, and pS6/S6 ratios) were significantly increased in EDL muscles of G rats, and the activation of p4E-BP1 was present in T rats. The fiber CSAs of the EDL muscles in T, G, and GT rats were increased compared to the C group. These changes were accompanied by a reduction in the 26 proteasome activity of EDL muscles from T rats. CONCLUSION: Five weeks of GS and/or RET induced muscle hypertrophy, as indicated by the increased CSAs of the EDL muscle fibers. The increase in CSA was mediated via the upregulated phosphorylation of Akt, 4E-BP1, p70S6k, and S6 in G animals and 4E-BP1 in T animals. In the EDL muscles from T animals, a decrease in proteasome activity, favoring a further increase in the CSA of the muscle fibers, was reported.
- ItemEditorial: Spotlight on aging: physiology, prevention, and management of skeletal muscle atrophy.(Frontiers Media S.A., 2023-12-05) Marzuca-Nassr GN; Peñailillo L; Valladares-Ide D; Martinez-Huenchullan S; Curi R; Hirabara SM; Vitzel KF; D'Antona G
- ItemEndoplasmic Reticulum Stress and Autophagy Markers in Soleus Muscle Disuse-Induced Atrophy of Rats Treated with Fish Oil(MDPI (Basel, Switzerland), 2021-07) Marzuca-Nassr GN; Kuwabara WMT; Vitzel KF; Murata GM; Torres RP; Mancini-Filho J; Alba-Loureiro TC; Curi REndoplasmic reticulum stress (ERS) and autophagy pathways are implicated in disuse muscle atrophy. The effects of high eicosapentaenoic (EPA) or high docosahexaenoic (DHA) fish oils on soleus muscle ERS and autophagy markers were investigated in a rat hindlimb suspension (HS) atrophy model. Adult Wistar male rats received daily by gavage supplementation (0.3 mL per 100 g b.w.) of mineral oil or high EPA or high DHA fish oils (FOs) for two weeks. Afterward, the rats were subjected to HS and the respective treatments concomitantly for an additional two-week period. After four weeks, we evaluated ERS and autophagy markers in the soleus muscle. Results were analyzed using two-way analysis of variance (ANOVA) and Bonferroni post hoc test. Gastrocnemius muscle ω-6/ω-3 fatty acids (FAs) ratio was decreased by both FOs indicating the tissue incorporation of omega-3 fatty acids. HS altered (p < 0.05) the protein content (decreasing total p38 and BiP and increasing p-JNK2/total JNK2 ratio, and caspase 3) and gene expressions (decreasing BiP and increasing IRE1 and PERK) of ERS and autophagy (decreasing Beclin and increasing LC3 and ATG14) markers in soleus. Both FOs attenuated (p < 0.05) the increase in PERK and ATG14 expressions induced by HS. Thus, both FOs could potentially attenuate ERS and autophagy in skeletal muscles undergoing atrophy.
- ItemMaternal low-protein diet reduces skeletal muscle protein synthesis and mass via Akt-mTOR pathway in adult rats(Frontiers Media S.A., 2022) de Vasconcelos DAA; Nachbar RT; Pinheiro CH; do Amaral CL; Crisma AR; Vitzel KF; Abreu P; Alonso-Vale MI; Lopes AB; Bento-Santos A; Falcão-Tebas F; de Santana DF; do Nascimento E; Curi R; Pithon-Curi TC; Hirabara SM; Leandro CGSeveral studies have demonstrated that a maternal low-protein diet induces long-term metabolic disorders, but the involved mechanisms are unclear. This study investigated the molecular effects of a low-protein diet during pregnancy and lactation on glucose and protein metabolism in soleus muscle isolated from adult male rats. Female rats were fed either a normal protein diet or low-protein diet during gestation and lactation. After weaning, all pups were fed a normal protein diet until the 210th day postpartum. In the 7th month of life, mass, contractile function, protein and glucose metabolism, and the Akt-mTOR pathway were measured in the soleus muscles of male pups. Dry weight and contractile function of soleus muscle in the low-protein diet group rats were found to be lower compared to the control group. Lipid synthesis was evaluated by measuring palmitate incorporation in white adipose tissue. Palmitate incorporation was higher in the white adipose tissue of the low-protein diet group. When incubated soleus muscles were stimulated with insulin, protein synthesis, total amino acid incorporation and free amino acid content, glucose incorporation and uptake, and glycogen synthesis were found to be reduced in low-protein diet group rats. Fasting glycemia was higher in the low-protein diet group. These metabolic changes were associated with a decrease in Akt and GSK-3β signaling responses to insulin and a reduction in RPS6 in the absence of the hormone. There was also notably lower expression of Akt in the isolated soleus muscle of low-protein diet group rats. This study is the first to demonstrate how maternal diet restriction can reduce skeletal muscle protein and mass by downregulating the Akt-mTOR pathway in adulthood.
- ItemMolecular and cellular mechanisms involved in tissue-specific metabolic modulation by SARS-CoV-2(Frontiers Media SA, 2022) dos Santos AAC; Rodrigues LE; Alecrim-Zeza AL; de Araújo Ferreira L; Trettel CDS; Gimenes GM; da Silva AF; Sousa-Filho CPB; Serdan TDA; Levada-Pires AC; Hatanaka E; Borges FT; de Barros MP; Cury-Boaventura MF; Bertolini GL; Cassolla P; Marzuca-Nassr GN; Vitzel KF; Pithon-Curi TC; Masi LN; Curi R; Gorjao R; Hirabara SMCoronavirus disease 2019 (COVID-19) is triggered by the SARS-CoV-2, which is able to infect and cause dysfunction not only in lungs, but also in multiple organs, including central nervous system, skeletal muscle, kidneys, heart, liver, and intestine. Several metabolic disturbances are associated with cell damage or tissue injury, but the mechanisms involved are not yet fully elucidated. Some potential mechanisms involved in the COVID-19-induced tissue dysfunction are proposed, such as: (a) High expression and levels of proinflammatory cytokines, including TNF-α IL-6, IL-1β, INF-α and INF-β, increasing the systemic and tissue inflammatory state; (b) Induction of oxidative stress due to redox imbalance, resulting in cell injury or death induced by elevated production of reactive oxygen species; and (c) Deregulation of the renin-angiotensin-aldosterone system, exacerbating the inflammatory and oxidative stress responses. In this review, we discuss the main metabolic disturbances observed in different target tissues of SARS-CoV-2 and the potential mechanisms involved in these changes associated with the tissue dysfunction.
- ItemSkeletal muscle mass, strength, and physical performance gains are similar between healthy postmenopausal women and postmenopausal breast cancer survivors after 12 weeks of resistance exercise training.(Springer Nature, 2024-11-23) Artigas-Arias M; Alegría-Molina A; Vidal-Seguel N; Muñoz-Cofre R; Carranza-Leiva J; Sepúlveda-Lara A; Vitzel KF; Huard N; Sapunar J; Salazar LA; Curi R; Marzuca-Nassr GNPurpose Resistance exercise training (RET) effectively increases skeletal muscle mass and strength in healthy postmenopausal women. However, its effects on these parameters in postmenopausal breast cancer survivors are controversial or limited. Therefore, the aim of this study was to compare the effects of a 12-week progressive whole-body RET program on skeletal muscle mass, strength, and physical performance in healthy postmenopausal women versus postmenopausal women who survived breast cancer. Methods Thirteen healthy postmenopausal women (HEA, 54 ± 3 years, BMI 26.6 ± 2.7 kg·m2, n = 13) and eleven postmenopausal breast cancer survivors (BCS, 52 ± 5 years, BMI 26.8 ± 2.1 kg·m2, n = 11) participated in the study. Before and after the RET program, evaluations were performed on quadriceps muscle thickness, one-repetition maximum strength (1RM) for various exercises, grip strength, and physical performance. Results Both groups showed significant improvements in quadriceps muscle thickness (time effect, P < 0.001); 1RM strength for leg extension, leg press, chest press, horizontal row, and elbow extension (time effect, all P < 0.001); as well as handgrip strength (time effect, P = 0.035) and physical performance (time effect, all P < 0.001) after the 12-week RET program. There were no significant differences between the groups in response to RET for any of the outcomes measured. Conclusion Twelve weeks of RET significantly increases skeletal muscle mass, strength, and physical performance in postmenopausal women. No differences were observed between healthy postmenopausal women and postmenopausal breast cancer survivors. These findings point out that this study’s RET promotes skeletal muscle mass, strength, and performance gains regardless of breast cancer. Pre-Print Platform Research Square: https://doi.org/10.21203/rs.3.rs-4145715/v1; https://www.researchsquare.com/article/rs-4145715/v1 Clinical trial registration: NCT05690295.