Browsing by Author "Cantin, Claudette"

Now showing 1 - 4 of 4
  • No Thumbnail Available
    Item
    A single bout of resistance exercise triggers mitophagy, potentially involving the ejection of mitochondria in human skeletal muscle
    (2024) Diaz-Castro, Francisco; Tunon-Suarez, Mauro; Rivera, Patricia; Botella, Javier; Cancino, Jorge; Figueroa, Ana Maria; Gutierrez, Juan; Cantin, Claudette; Deldicque, Louise; Zbinden-Foncea, Hermann; Nielsen, Joachim; Henriquez-Olguin, Carlos; Morselli, Eugenia; Castro-Sepulveda, Mauricio
    AimThe present study aimed to investigate the effects of a single bout of resistance exercise on mitophagy in human skeletal muscle (SkM).MethodsEight healthy men were recruited to complete an acute bout of one-leg resistance exercise. SkM biopsies were obtained one hour after exercise in the resting leg (Rest-leg) and the contracting leg (Ex-leg). Mitophagy was assessed using protein-related abundance, transmission electron microscopy (TEM), and fluorescence microscopy.ResultsOur results show that acute resistance exercise increased pro-fission protein phosphorylation (DRP1Ser616) and decreased mitophagy markers such as PARKIN and BNIP3L/NIX protein abundance in the Ex-leg. Additionally, mitochondrial complex IV decreased in the Ex-leg when compared to the Rest-leg. In the Ex-leg, TEM and immunofluorescence images showed mitochondrial cristae abnormalities, a mitochondrial fission phenotype, and increased mitophagosome-like structures in both subsarcolemmal and intermyofibrillar mitochondria. We also observed increased mitophagosome-like structures on the subsarcolemmal cleft and mitochondria in the extracellular space of SkM in the Ex-leg. We stimulated human primary myotubes with CCCP, which mimics mitophagy induction in the Ex-leg, and found that BNIP3L/NIX protein abundance decreased independently of lysosomal degradation. Finally, in another human cohort, we found a negative association between BNIP3L/NIX protein abundance with both mitophagosome-like structures and mitochondrial cristae density in the SkM.ConclusionThe findings suggest that a single bout of resistance exercise can initiate mitophagy, potentially involving mitochondrial ejection, in human skeletal muscle. BNIP3L/NIX is proposed as a sensitive marker for assessing mitophagy flux in SkM.
  • Thumbnail Image
    Item
    Adenosine receptors: Modulators of lipid availability that are controlled by lipid levels
    (2017) Leiva Mendoza, Andrea Alejandra; Guzmán Gutiérrez, Enrique; Contreras Duarte, Susana de las Mercedes; Fuenzalida Saavedra, Bárbara; Cantin, Claudette; Carvajal, Lorena; Salsoso Rodríguez, M. Rocío; Gutiérrez, Jaime; Pardo, Fabián; Sobrevía Luarte, Luis Alberto
  • No Thumbnail Available
    Item
    Cholesterol uptake and efflux are impaired in human trophoblast cells from pregnancies with maternal supraphysiological hypercholesterolemia
    (2020) Fuenzalida, Barbara; Cantin, Claudette; Kallol, Sampada; Carvajal, Lorena; Pasten, Valentina; Contreras-Duarte, Susana; Albrecht, Christiane; Gutierrez, Jaime; Leiva, Andrea
    Maternal physiological (MPH) or supraphysiological hypercholesterolaemia (MSPH) occurs during pregnancy. Cholesterol trafficking from maternal to foetal circulation requires the uptake of maternal LDL and HDL by syncytiotrophoblast and cholesterol efflux from this multinucleated tissue to ApoA-I and HDL. We aimed to determine the effects of MSPH on placental cholesterol trafficking. Placental tissue and primary human trophoblast (PHT) were isolated from pregnant women with total cholesterol <280 md/dL (MPH, n = 27) or >= 280 md/dL (MSPH, n = 28). The lipid profile in umbilical cord blood from MPH and MSPH neonates was similar. The abundance of LDL receptor (LDLR) and HDL receptor (SR-BI) was comparable between MSPH and MPH placentas. However, LDLR was localized mainly in the syncytiotrophoblast surface and was associated with reduced placental levels of its ligand ApoB. In PHT from MSPH, the uptake of LDL and HDL was lower compared to MPH, without changes in LDLR and reduced levels of SR-BI. Regarding cholesterol efflux, in MSPH placentas, the abundance of cholesterol transporter ABCA1 was increased, while ABCG1 and SR-BI were reduced. In PHT from MSPH, the cholesterol efflux to ApoA-I was increased and to HDL was reduced, along with reduced levels of ABCG1, compared to MPH. Inhibition of SR-BI did not change cholesterol efflux in PHT. The TC content in PHT was comparable in MPH and MSPH cells. However, free cholesterol was increased in MSPH cells. We conclude that MSPH alters the trafficking and content of cholesterol in placental trophoblasts, which could be associated with changes in the placenta-mediated maternal-to-foetal cholesterol trafficking.
  • No Thumbnail Available
    Item
    Small extracellular vesicles from pregnant women with maternal supraphysiological hypercholesterolemia impair endothelial cell function in vitro
    (2023) Contreras-Duarte, Susana; Escalona-Rivano, Rodrigo; Cantin, Claudette; Valdivia, Pascuala; Zapata, David; Carvajal, Lorena; Brito, Roberto; Cerda, Alvaro; Illanes, Sebastian; Gutierrez, Jaime; Leiva, Andrea
    Maternal physiological hypercholesterolemia MPH, maternal total cholesterol (TC) levels at term of pregnancy <280 mg/dL) occurs to assure fetal development. Maternal supraphysiological hypercholesterolemia (MSPH, TC levels >280 mg/dL) is a pathological condition associated with maternal, placental, and fetal endothelial dysfunction and early neonatal atherosclerosis development. Small extracellular vesicles (sEVs) are delivered to the extracellular space by different cells, where they modulate cell functions by transporting active signaling molecules, including proteins and miRNA.Aim: To determine whether sEVs from MSPH women could alter the function of endothelial cells (angiogenesis, endothelial activation and nitric oxide synthesis capacity).Methods: This study included 24 Chilean women (12 MPH and 12 MSPH). sEVs were isolated from maternal plasma and characterized by sEV markers (CD9, Alix and HSP70), nanoparticle tracking analysis, transmission electron microscopy, and protein and cholesterol content. The endothelial cell line HMEC-1 was used to determine the uptake of labeled sEVs and the effects of sEVs on cell viability, endothelial tube formation, endothelial cell activation, and endothelial nitric oxide expression and function.Results: In MSPH women, the plasma concentration of sEVs was increased compared to that in MPH women. MSPH-sEVs were highly taken up by HMEC-1 cells and reduced angiogenic capacity and the expression and activity of eNOS without changing cell viability or endothelial activation compared to MPH-sEVs. Conclusion: sEVs from MSPH women impair angiogenesis and nitric oxide synthesis in endothelial cells, which could contribute to MSPH-associated endothelial dysfunction.