Browsing by Author "Burboa, Pia C."

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    Novel Pannexin-1-Coupled Signaling Cascade Involved in the Control of Endothelial Cell Function and NO-Dependent Relaxation
    (2021) Lillo, Mauricio A.; Gaete, Pablo S.; Puebla, Mariela; Burboa, Pia C.; Poblete, Ines; Figueroa, Xavier F.
    Deletion of pannexin-1 (Panx-1) leads not only to a reduction in endothelium-derived hyperpolarization but also to an increase in NO-mediated vasodilation. Therefore, we evaluated the participation of Panx-1-formed channels in the control of membrane potential and [Ca2+](i) of endothelial cells. Changes in NO-mediated vasodilation, membrane potential, superoxide anion (O-2(-)) formation, and endothelial cell [Ca2+](i) were analyzed in rat isolated mesenteric arterial beds and primary cultures of mesenteric endothelial cells. Inhibition of Panx-1 channels with probenecid (1 mM) or the Panx-1 blocking peptide (10)Panx (60 mu M) evoked an increase in the ACh (100 nM)-induced vasodilation of KCl-contracted mesenteries and in the phosphorylation level of endothelial NO synthase (eNOS) at serine 1177 (P-eNOS(S1177)) and Akt at serine 473 (P-Akt(S473)). In addition, probenecid or (10)Panx application activated a rapid, tetrodotoxin (TTX, 300 nM)-sensitive, membrane potential depolarization and [Ca2+](i) increase in endothelial cells. Interestingly, the endothelial cell depolarization was converted into a transient spike after removing Ca2+ ions from the buffer solution and in the presence of 100 mu M mibefradil or 10 mu M Ni2+. As expected, Ni2+ also abolished the increment in [Ca2+](i). Expression of Na(v)1.2, Na(v)1.6, and Ca(v)3.2 isoforms of voltage-dependent Na+ and Ca2+ channels was confirmed by immunocytochemistry. Furthermore, the Panx-1 channel blockade was associated with an increase in O-2(-) production. Treatment with 10 mu M TEMPOL or 100 mu M apocynin prevented the increase in O-2(-) formation, ACh-induced vasodilation, P-eNOS(S1177), and P-Akt(S473) observed in response to Panx-1 inhibition. These findings indicate that the Panx-1 channel blockade triggers a novel complex signaling pathway initiated by the sequential activation of TTX-sensitive Na-v channels and Ca(v)3.2 channels, leading to an increase in NO-mediated vasodilation through a NADPH oxidase-dependent P-eNOS(S1177), which suggests that Panx-1 may be involved in the endothelium-dependent control of arterial blood pressure.
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    UiO-66(Zr) as drug delivery system for non-steroidal anti-inflammatory drugs
    (2024) Salazar, Javier; Hidalgo-Rosa, Yoan; Burboa, Pia C.; Wu, Yi-nan; Escalona, Nesor; Leiva, Angel; Zarate, Ximena; Schott, Eduardo
    The toxicity for the human body of non-steroidal anti-inflammatory drugs (NSAIDs) overdoses is a consequence of their low water solubility, high doses, and facile accessibility to the population. New drug delivery systems (DDS) are necessary to overcome the bioavailability and toxicity related to NSAIDs. In this context, UiO-66(Zr) metal-organic framework (MOF) shows high porosity, stability, and load capacity, thus being a promising DDS. However, the adsorption and release capability for different NSAIDs is scarcely described. In this work, the biocompatible UiO-66(Zr) MOF was used to study the adsorption and release conditions of ibuprofen, naproxen, and diclofenac using a theoretical and experimental approximation. DFT results showed that the MOF-drug interaction was due to an intermolecular hydrogen bond between protons of the groups in the defect sites, (mu 3 - OH, and - OH2) and a lone pair of oxygen carboxyl functional group of the NSAIDs. Also, the experimental results suggest that the solvent where the drug is dissolved affects the adsorption process. The adsorption kinetics are similar between the drugs, but the maximum load capacity differs for each drug. The release kinetics assay showed a solvent dependence kinetics whose maximum liberation capacity is affected by the interaction between the drug and the material. Finally, the biological assays show that none of the systems studied are cytotoxic for HMVEC. Additionally, the wound healing assay suggests that the UiO-66(Zr) material has potential application on the wound healing process. However, further studies should be done.