Browsing by Author "Simon, Felipe"
Now showing 1 - 12 of 12
Results Per Page
Sort Options
- ItemAngiotensin-(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
- ItemCentral 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
- ItemCholic 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, ClaudioBackground: 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.
- ItemCirculating Endothelial Cells From Septic Shock Patients Convert to Fibroblasts Are Associated With the Resuscitation Fluid Dose and Are Biomarkers for Survival Prediction.(2019) Tapia, Pablo; Gatica, Sebastian; Cortés-Rivera, Cristian; Otero, Carolina; Becerra, Álvaro; Riedel, Claudia A.; Cabello-Verrugio, Claudio; Kalergis, Alexis M.; Simon, FelipeOBJECTIVES:To determine whether circulating endothelial cells from septic shock patients and from nonseptic shock patients are transformed in activated fibroblast by changing the expression level of endothelial and fibrotic proteins, whether the level of the protein expression change is associated with the amount of administered resuscitation fluid, and whether this circulating endothelial cell protein expression change is a biomarker to predict sepsis survival. DESIGN:Prospective study. SETTING:Medical-surgical ICUs in a tertiary care hospital. PATIENTS:Forty-three patients admitted in ICU and 22 healthy volunteers. INTERVENTIONS:None. MEASUREMENTS AND MAIN RESULTS:Circulating mature endothelial cells and circulating endothelial progenitor cells from septic shock and nonseptic shock patients showed evidence of endothelial fibrosis by changing the endothelial protein expression pattern. The endothelial proteins were downregulated, whereas fibroblast-specific markers were increased. The magnitude of the expression change in endothelial and fibrotic proteins was higher in the septic shock nonsurvivors patients but not in nonseptic shock. Interestingly, the decrease in the endothelial protein expression was correlated with the administered resuscitation fluid better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in the septic shock nonsurvivors patients but not in nonseptic shock. Notably, the significant difference between endothelial and fibrotic protein expression indicated a nonsurvival outcome in septic shock but not in nonseptic shock patients. Remarkably, area under the receiver operating characteristic curve analysis showed that endothelial protein expression levels predicted the survival outcome better than the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores in septic shock but not in nonseptic shock patients. CONCLUSIONS:Circulating endothelial cells from septic shock patients are acutely converted into fibroblasts. Endothelial and fibrotic protein expression level are associated with resuscitation fluid administration magnitude and can be used as biomarkers for an early survival diagnosis of sepsis.
- ItemCritical contribution of Na+-Ca2+ exchanger to the Ca2+-mediated vasodilation activated in endothelial cells of resistance arteries(2018) Lillo, Mauricio A.; Gaete, Pablo S.; Puebla, Mariela; Ardiles, Nicolas M.; Poblete, Ines; Becerra, Alvaro; Simon, Felipe; Figueroa, Xavier
- ItemEndotoxin-Induced Endothelial Fibrosis Is Dependent on Expression of Transforming Growth Factors beta 1 and beta 2(2014) Echeverría, César; Montorfano, Ignacio; Tapia, Pablo; Riedel, Claudia; Cabello Verrugio, Claudio Alejandro; Simon, Felipe
- ItemEndotoxin-induced skeletal muscle wasting is prevented by angiotensin-(1-7) through a p38 MAPK-dependent mechanism(2015) Morales, María Gabriela; Olguín Marín, Hugo César; Di Capua, Gabriella; Brandan, Enrique; Simon, Felipe; Cabello Verrugio, Claudio Alejandro; Morales, María Gabriela; Olguín Marín, Hugo César; Di Capua, Gabriella; Brandan, Enrique; Simon, Felipe; Cabello Verrugio, Claudio Alejandro
- ItemHigh 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
- ItemPreventive leptin administration protects against sepsis through improving hypotension, tachycardia, oxidative stress burst, multiple organ dysfunction, and increasing survival(2018) Vallejos, Alejandro; Olivares, Pedro; Varela, Diego; Echeverria, Cesar; Cabello Verrugio, Claudio Alejandro; Pérez Leighton, Claudio; Simon, Felipe
- ItemSarcopenia 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
- ItemTGF-β requires the activation of canonical and non-canonical signalling pathways to induce skeletal muscle atrophy(2018) Ábrigo, Johanna; Campos, Fabian; Simon, Felipe; Riedel, Claudia; Cabrera García, Daniel Alejandro; Vilos, Cristian; Cabello Verrugio, Claudio Alejandro
- ItemTransforming 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