Browsing by Author "Morales, Bernardo"

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    ATP and adenosine trigger the interaction of plasma membrane IP3 receptors with protein kinase A in oviductal ciliated cells
    (2007) Barrera, Nelson P.; Morales, Bernardo; Villalon, Manuel
    We have demonstrated that adenosine did not produce any change of intracellular free Ca2+ concentration ([Ca2+]i) in oviductal ciliated cells; however, it increased the ATP-induced Ca2+ influx through the activation of protein kinase A (PKA). Uncaging Of IP3 and cAMP triggered a larger Ca2+ influx than did IP3 alone. Furthermore, the IP3 effect was abolished by Xestospongin C, an IP3 receptor blocker. Whole-cell recordings demonstrated the presence of an ATP-induced Ca2+ current, and the addition of adenosine increased the peak of this current. This effect was not observed in the presence of H-89, a PKA inhibitor. Using excised macro-patches of plasma membrane, IP3 generated a current, which was higher in the presence of the catalytic PKA subunit and this current was blocked by Xestospongin C. We show here that activation of plasma membrane IP3 receptors directly triggers Ca2+ influx in response to ATP and that these receptors are modulated by adenosine-activated PKA. (C) 2007 Elsevier Inc. All rights reserved.
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    Extracellular Vesicles derived from Apis mellifera Royal Jelly promote wound healing by modulating inflammation and cellular responses
    (2022) Álvarez, Simón; Contreras Kallens, Pamina; Aguayo Paul, Sebastián; Ramírez, Orlando; Vallejos, Catalina; Ruiz, Jorge; Carrasco Gallardo, Eva; Troncoso Vera, Stephanie; Morales, Bernardo; Schuh, Christina
    Apis mellifera Royal Jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. Several active compounds have been identified, however, the mechanisms of action still remain widely unknown. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs) and in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing associated effects. Molecular analysis of RJEVs verified the presence of important conserved exosomal markers such as CD63 and syntenin, as well as cargo molecules MRJP1, defensin-1 and jellein-3. RJEV internalization analysis demonstrated the involvement of membrane fusion as well as macropinocytosis or clathrin-dependent endocytosis into mammalian cells. Furthermore, RJEVs have demonstrated to modulate MSCs differentiation and secretome, as well as decrease LPS-induced inflammation in RAW 264.7 macrophages by blocking the MAPK pathway. In vivo studies confirmed anti-bacterial effects of RJEVs, and demonstrated an acceleration of wound healing in a splinted mouse model. Summarizing, this study suggests that RJEVs of potentially exosomal origin play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing.
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    Royal jelly extracellular vesicles promote wound healing by modulating underlying cellular responses
    (2023) Álvarez, Simón; Contreras-Kallen, Pamina; Aguayo Paul, Sebastián; Ramírez, Orlando; Vallejos, Catalina; Ruiz, Jorge; Carrasco-Gallardo, Eva; Troncoso-Vera, Stefanie; Morales, Bernardo; Schuh, Christina M.A.P.
    Apis mellifera royal jelly (RJ) is a well-known remedy in traditional medicine around the world and its versatile effects range from antibacterial to anti-inflammatory properties and pro-regenerative properties. As a glandular product, RJ has been shown to contain a substantial number of extracellular vesicles (EVs), and, in this study, we aimed to investigate the extent of involvement of RJEVs in wound healing-associated effects. Molecular analysis of RJEVs verified the presence of exosomal markers such as CD63 and syntenin, and cargo molecules MRJP1, defensin-1, and jellein-3. Furthermore, RJEVs were demonstrated to modulate mesenchymal stem cell (MSC) differentiation and secretome, as well as decrease LPS-induced inflammation in macrophages by blocking the mitogen-activated protein kinase (MAPK) pathway. In vivo studies confirmed antibacterial effects of RJEVs and demonstrated an acceleration of wound healing in a splinted mouse model. This study suggests that RJEVs play a crucial role in the known effects of RJ by modulating the inflammatory phase and cellular response in wound healing. Transfer of RJ into the clinics has been impeded by the high complexity of the raw material. Isolating EVs from the raw RJ decreases the complexity while allowing standardization and quality control, bringing a natural nano-therapy one step closer to the clinics.
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    The release of sympathetic neurotransmitters is impaired in aged rats after an inflammatory stimulus: A possible link between cytokine production and sympathetic transmission
    (ELSEVIER IRELAND LTD, 2008) Donoso, Veronica; Gomez, Christian R.; Orriantia, Miguel Angel; Perez, Viviana; Torres, Claudio; Coddou, Claudio; Nelson, Pablo; Maisey, Kevin; Morales, Bernardo; Fernandez, Ricardo; Imarai, Monica; Huidobro Toro, Juan Pablo; Sierra, Felipe; Acuna Castillo, Claudio
    Aging results in a general decline in the response to external insults, including acute inflammatory challenges. In young animals, the inflammatory response requires activation of the sympathetic system, including neurotransmitters Such as ATP, and catecholamines (epinephrine and norepinephrine). To test whether aging affects activation of this axis, and whether this in turn might affect cytokine release, we administered lipopolysaccharide (LPS) i.p. to adult, middle-aged and aged Fisher 344 rats (6-, 15- and 23-month old, respectively) and evaluated the early (0-12 h) serum levels of Neuropeptide-Y (NP-Y), ATP and vanillyl mandelic acid (VMA, as in indirect measurement of catecholamine levels). In addition, we evaluated the association between these factors and serum levels of the cytokines tumor necrosis factor-alpha (TNF alpha) and interleukin-10 (IL-10). Induction of both ATP and NP-Y was markedly reduced in the serum of aged animals, when compared to their younger Counterparts, while induction of VMA was not affected by age. in spite of these changes, serum levels of TNF alpha and IL-10 were strongly hyper induced and delayed in aged rats. The results suggest that during aging there is a dys-regulation in sympathetic neurotransmitter regulatory Mechanisms, and this might play a role in the impairment of the inflammatory response. (C) 2008 Elsevier Ireland Ltd. All rights reserved.