Browsing by Author "Abrigo, Johanna"

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    Angiotensin-(1-7) improves skeletal muscle regeneration
    (2023) Valero-Breton, Mayalen; Tacchi, Franco; Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Cabello-Verrugio, Claudio
    Skeletal muscle possesses regenerative potential via satellite cells, compromised in muscular dystrophies leading to fibrosis and fat infiltration. Angiotensin II (Ang-II) is commonly associated with pathological states. In contrast, Angiotensin (1-7) [Ang-(1-7)] counters Ang-II, acting via the Mas receptor. While Ang-II affects skeletal muscle regeneration, the influence of Ang-(1-7) remains to be elucidated. Therefore, this study aims to investigate the role of Ang-(17) in skeletal muscle regeneration. C2C12 cells were differentiated in the absence or presence of 10 nM of Ang-(1-7). The diameter of myotubes and protein levels of myogenin and myosin heavy chain (MHC) were determined. C57BL/6 WT male mice 16-18 weeks old) were randomly assigned to injury-vehicle, injury-Ang-(1-7), and control groups. Ang-(1-7) was administered via osmotic pumps, and muscle injury was induced by injecting barium chloride to assess muscle regeneration through histological analyses. Moreover, embryonic myosin (eMHC) and myogenin protein levels were evaluated. C2C12 myotubes incubated with Ang-(1-7) showed larger diameters than the untreated group and increased myogenin and MHC protein levels during differentiation. Ang-(1-7) administration enhances regeneration by promoting a larger diameter of new muscle fibers. Furthermore, higher numbers of eMHC (+) fibers were observed in the injured-Ang-(1-7), which also had a larger diameter. Moreover, eMHC and myogenin protein levels were elevated, supporting enhanced regeneration due to Ang-(1-7) administration. Ang-(1-7) effectively promotes differentiation in vitro and improves muscle regeneration in the context of injuries, with potential implications for treating muscle-related disorders.
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    Angiotensin-(1-7) Prevents Skeletal Muscle Atrophy Induced by Transforming Growth Factor Type Beta (TGF-beta) via Mas Receptor Activation
    (2016) Abrigo, Johanna; Simon, Felipe; Cabrera García, Daniel Alejandro; Cabello Verrugio, Claudio Alejandro
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    Bile Acids Induce Alterations in Mitochondrial Function in Skeletal Muscle Fibers
    (2022) Abrigo, Johanna; Olguin, Hugo; Gutierrez, Danae; Tacchi, Franco; Arrese, Marco; Cabrera, Daniel; Valero-Breton, Mayalen; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, Claudio
    Cholestatic chronic liver disease is characterized by developing sarcopenia and elevated serum levels of bile acids. Sarcopenia is a skeletal muscle disorder with the hallmarks of muscle weakness, muscle mass loss, and muscle strength decline. Our previous report demonstrated that deoxycholic acid (DCA) and cholic acid (CA), through the membrane receptor TGR5, induce a sarcopenia-like phenotype in myotubes and muscle fibers. The present study aimed to evaluate the impact of DCA and CA on mitochondrial mass and function in muscle fibers and the role of the TGR5 receptor. To this end, muscle fibers obtained from wild-type and TGR5(-/-) mice were incubated with DCA and CA. Our results indicated that DCA and CA decreased mitochondrial mass, DNA, and potential in a TGR5-dependent fashion. Furthermore, with TGR5 participation, DCA and CA also reduced the oxygen consumption rate and complexes I and II from the mitochondrial electron transport chain. In addition, DCA and CA generated more mitochondrial reactive oxygen species than the control, which were abolished in TGR5(-/-) mice muscle fibers. Our results indicate that DCA and CA induce mitochondrial dysfunction in muscle fibers through a TGR5-dependent mechanism.
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    Central Role of Transforming Growth Factor Type Beta 1 in Skeletal Muscle Dysfunctions: An Update on Therapeutic Strategies
    (2018) Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Cordova, Gonzalo; Trollet, Capucine; Cabello Verrugio, Claudio Alejandro
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    Cholic and deoxycholic acids induce mitochondrial dysfunction, impaired biogenesis and autophagic fux in skeletal muscle cells
    (2023) Abrigo, Johanna; Olguín Marín, Hugo César; Tacchi, Franco; Orozco-Aguilar, Josué; Valero-Breton, Mayalen; Soto Ramírez, Jorge Andrés; Castro-Sepúlveda, Mauricio; Elorza, Alvaro A.; Simon, Felipe; Cabello-Verrugio, Claudio
    Background: Skeletal muscle is sensitive to bile acids (BA) because it expresses the TGR5 receptor for BA. Cholic (CA) and deoxycholic (DCA) acids induce a sarcopenia-like phenotype through TGR5-dependent mechanisms. Besides, a mouse model of cholestasis-induced sarcopenia was characterised by increased levels of serum BA and muscle weakness, alterations that are dependent on TGR5 expression. Mitochondrial alterations, such as decreased mitochondrial potential and oxygen consumption rate (OCR), increased mitochondrial reactive oxygen species (mtROS) and unbalanced biogenesis and mitophagy, have not been studied in BA-induced sarcopenia. Methods: We evaluated the effects of DCA and CA on mitochondrial alterations in C2C12 myotubes and a mouse model of cholestasis-induced sarcopenia. We measured mitochondrial mass by TOM20 levels and mitochondrial DNA; ultrastructural alterations by transmission electronic microscopy; mitochondrial biogenesis by PGC-1α plasmid reporter activity and protein levels by western blot analysis; mitophagy by the co-localisation of the MitoTracker and LysoTracker fluorescent probes; mitochondrial potential by detecting the TMRE probe signal; protein levels of OXPHOS complexes and LC3B by western blot analysis; OCR by Seahorse measures; and mtROS by MitoSOX probe signals. Results: DCA and CA caused a reduction in mitochondrial mass and decreased mitochondrial biogenesis. Interestingly, DCA and CA increased LC3II/LC3I ratio and decreased autophagic flux concordant with raised mitophagosome-like structures. In addition, DCA and CA decreased mitochondrial potential and reduced protein levels in OXPHOS complexes I and II. The results also demonstrated that DCA and CA decreased basal, ATP-linked, FCCP-induced maximal respiration and spare OCR. DCA and CA also reduced the number of cristae. In addition, DCA and CA increased the mtROS. In mice with cholestasis-induced sarcopenia, TOM20, OXPHOS complexes I, II and III, and OCR were diminished. Interestingly, the OCR and OXPHOS complexes were correlated with muscle strength and bile acid levels. Conclusion: Our results showed that DCA and CA decreased mitochondrial mass, possibly by reducing mitochondrial biogenesis, which affects mitochondrial function, thereby altering potential OCR and mtROS generation. Some mitochondrial alterations were also observed in a mouse model of cholestasis-induced sarcopenia characterised by increased levels of BA, such as DCA and CA.
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    Combined Administration of Andrographolide and Angiotensin- (1-7) Synergically Increases the Muscle Function and Strength in Aged Mice
    (2022) Abrigo, Johanna; Simon, Felipe; Cabrera, Daniel; Vilos, Cristian; Cabello-Verrugio, Claudio
    Background: Sarcopenia is a progressive and generalized skeletal muscle disorder characterized by muscle weakness, loss of muscle mass, and decline in the capacity of force generation. Aging can cause sarcopenia. Several therapeutic strategies have been evaluated to prevent or alleviate this disorder. One of them is angiotensin 1-7 [Ang-(1-7)], an anti-atrophic peptide for skeletal muscles that regulates decreased muscle mass for several causes, including aging. Another regulator of muscle mass and function is andrographolide, a bicyclic diterpenoid lactone that decreases the nuclear factor kappa B (NF-kappa B) signaling and attenuates the severity of some muscle diseases. Objective: Evaluate the effect of combined administration of Ang-(1-7) with andrographolide on the physical performance, muscle strength, and fiber ' s diameter in a murine model of sarcopenia by aging. Methods: Aged male mice of the C57BL/6J strain were treated with Andrographolide, Ang-(1-7), or combined for three months. The physical performance, muscle strength, and fiber ' s diameter were measured. Results: The results showed that aged mice (24 months old) treated with Ang-(1-7) or Andrographolide improved their performance on a treadmill test, muscle strength, and their fiber ' s diameter compared to aged mice without treatment. The combined administration of Ang-(1-7) with andrographolide to aged mice has an enhanced synergically effect on physical performance, muscle strength, and fiber ' s diameter. Conclusion: Our results indicated that in aged mice, the effects of andrographolide and Ang-(1-7) on muscle function, strength, and fiber ' s diameter are potentiated.
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    High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration : Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis
    (2016) Abrigo, Johanna; Rivera, Juan Carlos; Aravena, Javier; Cabrera, Daniel; Simon, Felipe; Ezquer, Fernando; Ezquer, Marcelo; Cabello Verrugio, Claudio Alejandro
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    Sarcopenia in a mice model of chronic liver disease: role of the ubiquitin–proteasome system and oxidative stress
    (2018) Campos, Fabián; Abrigo, Johanna; Aguirre, Francisco; Garcés, Bruno; Arrese Jiménez, Marco; Karpen, Saúl; Cabrera, Daniel; Andía Kohnenkampf, Marcelo Edgardo; Simon, Felipe; Cabello Verrugio, Claudio Alejandro
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    Somatotropic Axis Dysfunction in Non-Alcoholic Fatty Liver Disease: Beneficial Hepatic and Systemic Effects of Hormone Supplementation
    (2018) Cabrera, Daniel; Cabello-Verrugio, Claudio; Solis, Nancy; San Martin, Diego; Cofre, Catalina; Pizarro, Margarita; Pablo Arab, Juan; Abrigo, Johanna; Campos, Fabian; Irigoyen, Betzabe; Carrasco-Avino, Gonzalo; Bezares, Katiuska; Riquelme, Valentina; Riquelme, Arnoldo; Arrese, Marco; Barrera Martínez, Francisco
    Background: Somatotropic axis dysfunction associated with non-alcoholic fatty liver disease (NAFLD) has potential multisystemic detrimental effects. Here, we analysed the effects of growth hormone (GH) and insulin-like growth factor-1 (IGF-1) supplementation on liver histology, adipokine profile and muscle function in an NAFLD model. Methods: C57BL/6 mice were fed with a high fat diet (HFD) for 12 weeks and were separated into three groups treated for 4 weeks with: (1) High fat diet (HFD) (n = 10); (2) HFD + GH 9 g/g/d (n = 10); (3) HFD + IGF-1 0.02 mu g/g/d (n = 9). A control group fed a chow diet was included (n = 6). Liver histology, liver triglycerides content, serum alanine aminotransferase (ALT) activity, adiponectin and leptin serum levels, in vivo muscle strength, tetanic force and muscle fibre cross-sectional area (CSA) were measured. Results: HFD + GH and HFD + IGF-1 groups showed significantly lower ALT activity compared to HFD (p < 0.01). Liver triglyceride content in HFD + GH was decreased compared to HFD (p < 0.01). Histologic steatosis score was increased in HFD and HFD + GH group (p < 0.01), whereas HFD + IGF-1 presented no difference compared to the chow group (p = 0.3). HFD + GH group presented lower serum leptin and adiponectin levels compared to HFD. GH and IGF-1 supplementation therapy reverted HFD-induced reduction in muscle strength and CSA (sarcopenia). Conclusions: GH and IGF-1 supplementation induced significant improvement in liver steatosis, aminotransferases and sarcopenia in a diet-induced NAFLD model.
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    Transforming growth factor type beta (TGF-β) requires reactive oxygen species to induce skeletal muscle atrophy
    (2016) Abrigo, Johanna; Rivera, Juan Carlos; Simon, Felipe; Cabrera García, Daniel Alejandro; Cabello Verrugio, Claudio Alejandro