(FBIOyF) Departamento de Ciencias Fisiológicas - Artículo de Revista
URI permanente para esta colección
Examinar
Envíos recientes
Ítem Acceso Abierto Cholesterol can modulate mitochondrial aquaporin-8 expression in human hepatic cells(Wiley, 2017-03-20) Danielli, Mauro; Capiglioni, Alejo M.; Marrone, Julieta; Calamita, Giuseppe; Marinelli, Raúl A.Hepatocyte mitochondrial aquaporin-8 (mtAQP8) works as a multifunctional membrane channel protein that facilitates the uptake of ammonia for its detoxification to urea as well as the mitochondrial release of hydrogen peroxide. Since early oligonucleotide microarray studies in liver of cholesterol-fed mice showed an AQP8 downregulation, we tested whether alterations of cholesterol content per se modulate mtAQP8 expression in human hepatocyte-derived Huh-7 cells. Cholesterol loading with methyl-β-cyclodextrin (mβCD):cholesterol complexes downregulated the proteolytic activation of cholesterol-responsive sterol regulatory element-binding protein (SREBP) transcriptions factors 1 and 2, and the expression of the target gene 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Under such conditions, mtAQP8 mRNA and protein expressions were significantly reduced. In contrast, cholesterol depletion using mβCD alone increased SREBP-1 and 2 activation and upregulated HMGCR and mtAQP8 mRNA and protein expressions. The results suggest that cholesterol can regulate transcriptionally human hepatocyte mtAQP8 expression likely via SREBPs. The functional implications of our findings are discussed.Ítem Acceso Abierto Adenovirus-mediated human aquaporin-1 expression in hepatocytes improves lipopolysaccharide-induced cholestasis(John Wiley & Sons Inc, 2017-12) Marrone, Julieta; Danielli, Mauro; Gaspari, César Ismael; Marinelli, Raúl A.; http://orcid.org/0000-0003-2934-8863Lipopolysaccharides (LPS) are known to cause cholestasis in sepsis. There is evidence that a defective expression of canalicular aquaporin water channels contributes to bile secretory failure in LPS-induced cholestasis. Thus, we studied whether the hepatic adenovirus-mediated transfer of human aquaporin-1 gene (haqp1) can improve the cholestasis induced by LPS. Adenoviral vector encoding hAQP1 (AdhAQP1) or control vector was administered to rats by retrograde intrabiliary infusion. Hepatocyte canalicular hAQP1 expression was assessed by liver immunostaining and immunoblotting in purified plasma membranes. LPS reduced bile flow and biliary bile acid excretion by 30% and 45%, respectively. AdhAQP1-treatment normalized both bile flow and biliary bile acid excretion in LPS-induced cholestasis. Moreover, markedly elevated serum bile acid levels in cholestatic rats, were also normalized with the AdhAQP1 hepatic transduction. Bile flow and serum or biliary bile acids in normal rats were not significantly altered by AdhAQP1. AdhAQP1 delivery unaffected the downregulated protein expression of canalicular bile salt export pump (BSEP/ABCB11) in cholestasis, but improved its transport activity restoring reduced canalicular cholesterol content. Our data suggest that the adenovirus-mediated hepatocyte hAQP1 expression improves LPS-induced cholestasis in rats by stimulating the BSEP/ABCB11-mediated biliary bile acid excretion; a finding that might contribute to the understanding and treatment of sepsis-associated cholestatic diseases.Ítem Acceso Abierto Hepatic preneoplasia induction in male Wistar rats: histological studies up to five months post treatment(Sociedad Española de Patología Digestiva (SEPD), 2016-08) Pisani, Gerardo Bruno; Valenti, José Luis; Quintana, Alejandra BeatrizBackground: Liver preneoplasia development in rats can be mimicked by an initiation-promotion model that induces the appearance of altered hepatocyte foc (FAH). Aims: We compare two initiation-promotion models to evaluate the presence of FAH or additional hepatic pathologies in which other organs were affected up to five month post treatment. Material and methods: FAH were induced in male adult Wistar rats with two doses of dietylnitrosamine (DEN, 150 mg/kg bw) followed by 4 doses per week (3 weeks) of 2-acetylaminofluorene (2-AAF, 20 mg/kg bw) or with one dose of DEN (200 mg/kg bw) followed by 2 doses per week (3 weeks) of 2-AAF. DEN 150, DEN 200 and control mice (received the vehicle of the drugs) groups were compared. Rats were euthanized immediately after the last dose of 2-AAF, at 3, 4 and 5 months (n = 3 euthanasia times per group). Samples of livers, lungs, kidneys, pancreatic tissue and small bowel were processed for histological and immunohistochemical analysis. Results: FAH persisted for 5 months in all livers of the DEN groups. Three months after withdrawal of 2-AAF, one rat from the DEN 150 group developed fibrosis and 5 months after 2-AAF removal another rat from the same group presented a microscopic hyperplastic nodule. Only the lungs had damage compatible with lesions induced by gavage-related reflux in DEN groups. Conclusion: We concluded that up to five month post treatments, FAH persisted in all the livers from the DEN groups; livers from the DEN 200 group showed no other hepatic lesions besides FAH, and only the lungs suffered pathological alterations in both treated groups.Ítem Acceso Abierto Comparison of two chemical models to induce hepatic preneoplasia in male Wistar rats(Elsevier, 2015-03) Vera, Marina Cecilia; Pisani, Gerardo Bruno; Biancardi, María E.; Bottai, Hebe; Alvarez, María de Luján; Quintana, Alejandra BeatrizBackground. One established model to induce hepatic preneoplasia (HP) (DEN 150) uses diethylnitrosamine (DEN) as initiator agent and 2-acetylaminofluorene (2-AAF) as a promoter drug. In addition, both chemicals cause liver cholestasis and fibrosis. Aim. We compared DEN 150 model with another adapted by us, DEN 200 to simplify the first one and to evaluate the effectiveness of both treatments to induce HP in rats. Material and methods. Male Wistar rats were divided in 3 groups: controls; DEN 150 (rats received 2 doses of DEN, 150 mg/kg body weight, 2 weeks apart, and then 2-AAF, 20 mg/kg body weight, 4 doses per week during 3 weeks); and DEN 200 (rats received a single dose of DEN 200 mg/kg body weight, and 2 weeks apart 2-AAF, 20 mg/kg body weight, 2 doses per week during 3 weeks). Four hepatic enzymes, prothrombin time percentage, the number of bile ductules, total collagen amount, the number of altered hepatic foci (AHF) per liver and the percentage of liver occupied by foci were analyzed. Results. There were no differences in the number of AHF per liver between treated groups. Rats from DEN 200 group showed a significant diminution in the volume of liver occupied by foci. DEN 200 group had no fibrosis and better hemostatic conditions than DEN 150 group. Both groups developed cholestasis. Conclusion. In conclusion, both protocols are good alternatives to induce HP in rats and the new protocol proposed is an effective and a simple methodology to provide subclinic states of liver cancer.Ítem Acceso Abierto Data of ureagenesis from ammonia, glutamine and alanine, and mitochondrial aquaporin-8 expression in thioacetamide-treated hepatocytes(Elsevier, 2020-05) Capiglioni, Alejo M.; Alvarez, María de Luján; Marinelli, Raúl A.We present data about the synthesis of urea from different substrates, i.e., free ammonia, glutamine and alanine in primary cultured rat hepatocytes treated or untreated with the model hepatotoxic agent thioacetamide (TAA). We also provide data about the expression of mitochondrial aquaporin-8 (mtAQP8), a hepatocyte channel protein which facilitates ammonia diffusion into mitochondria to supply the urea cycle. Ammonia-derived ureagenesis was significantly inhibited by about 30% while that from the both amino acids resulted unaffected in TAA-treated hepatocytes. Protein expression of mtAQP8 was decreased by about 80% after TAA treatment. These data can be useful for the understanding of the mechanisms of drug-induced hepatic dysfunction.Ítem Acceso Abierto Adenoviral transfer of human Aquaporin-8 gene to mouse liver improves ammonia-derived ureagenesis(MDPI, 2023-06-02) Capiglioni, Alejo M.; Capitani, María Celeste; Marrone, Julieta; Marinelli, Raúl A.We previously reported that, in cultured hepatocytes, mitochondrial aquaporin-8 (AQP8) channels facilitate the conversion of ammonia to urea and that the expression of human AQP8 (hAQP8) enhances ammonia-derived ureagenesis. In this study, we evaluated whether hepatic gene transfer of hAQP8 improves detoxification of ammonia to urea in normal mice as well as in mice with impaired hepatocyte ammonia metabolism. A recombinant adenoviral (Ad) vector encoding hAQP8, AdhAQP8, or a control Ad vector was administered via retrograde infusion into the bile duct of the mice. Hepatocyte mitochondrial expression of hAQP8 was confirmed using confocal immunofluorescence and immunoblotting. The normal hAQP8-transduced mice showed decreased plasma ammonia and increased liver urea. Enhanced ureagenesis was confirmed via the NMR studies assessing the synthesis of 15N-labeled urea from 15N-labeled ammonia. In separate experiments, we made use of the model hepatotoxic agent, thioacetamide, to induce defective hepatic metabolism of ammonia in mice. The adenovirus-mediated mitochondrial expression of hAQP8 was able to restore normal ammonemia and ureagenesis in the liver of the mice. Our data suggest that hAQP8 gene transfer to mouse liver improves detoxification of ammonia to urea. This finding could help better understand and treat disorders with defective hepatic ammonia metabolism.Ítem Acceso Abierto Studies on the contribution of PPAR Gamma to tuberculosis physiopathology(Frontiers Media, 2023-04-28) Díaz, Ariana; D’Attilio, Luciano David; Penas, Federico; Bongiovanni, Bettina; Massa, Estefania; Cevey, Agata; Santucci, Natalia; Bottasso, Oscar; Goren, Nora; Bay, María LuisaIntroduction: Tuberculosis (TB) is a major health problem characterized by an immuno-endocrine imbalance: elevated plasma levels of cortisol and pro- and anti-in fl ammatory mediators, as well as reduced levels of dehydroepiandrosterone. The etiological agent, Mycobacterium tuberculosis (Mtb), is captured by pulmonary macrophages (Mf), whose activation is necessary to cope with the control of Mtb, however, excessive activation of the inflammatory response also leads to tissue damage. Glucocorticoids (GC) are critical elements to counteract the immunoinflammatory reaction, and peroxisome proliferator-activated receptors (PPARs) are also involved in this regard. The primary forms of these receptors are PPARϒ, PPARa, and PPARb/d, the former being the most involved in anti-inflammatory responses. In this work, we seek to gain some insight into the contribution of PPARϒ in immunoendocrine-metabolic interactions by focusing on clinical studies in pulmonary TB patients and in vitro experiments on a Mf cell line. Methods and results: We found that TB patients, at the time of diagnosis, showed increased expression of the PPARϒ transcript in their peripheral blood mononuclear cells, positively associated with circulating cortisol and related to disease severity. Given this background, we investigated the expression of PPARϒ (RT-qPCR) in radiation-killed Mtb-stimulated human Mf. The Mtb stimulation of Mf derived from the human line THP1 significantly increased the expression of PPARϒ, while the activation of this receptor by a specific agonist decreased the expression of pro- and anti-inflammatory cytokines (IL-1β and IL-10). As expected, the addition of GC to stimulated cultures reduced IL-1β production, while cortisol treatment together with the PPARϒ agonist lowered the levels of this proinflammatory cytokine in stimulated cultures. The addition of RU486, a glucocorticoid receptor antagonist, only reversed the inhibition produced by the addition of GC. Conclusion: The current results provide a stimulating background for further analysis of the interconnection between PPARs and steroid hormones in the context of Mtb infection.Ítem Acceso Abierto The immunoregulatory actions of DHEA in tuberculosis, a tool for therapeutic intervention?(Frontiers Media, 2022-06-06) Bongiovanni, Bettina; Díaz, Ariana; Santucci, Natalia; D’Attilio, Luciano David; Bottasso, Oscar; Hernández-Pando, Rogelio; Bay, María LuisaDehydroepiandrosterone (DHEA) is an androgen synthesized by the adrenal cortex, which is an intermediary in the biosynthesis of sex hormones, such as testosterone and estradiol. DHEA mostly circulates as a conjugated ester, in the form of sulfate (DHEAS). There exist several endogenous factors able to influence its synthesis, the most common ones being the corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), growth factors, and proinflammatory cytokines, among others. Like other steroid hormones, DHEA, can alter the functioning of immune cells and therefore the course of diseases exhibiting an immune-inflammatory component, mostly from autoimmune or infectious nature. We herein review the role played by DHEA during a major infectious disease like tuberculosis (TB). Data recorded from TB patients, mouse models, or in vitro studies show that DHEA is likely to be implied in better disease control. This provides a stimulating background for carrying out clinical studies aimed at assessing the usefulness of DHEA as an adjuvant in TB patients.Ítem Acceso Abierto Extracellular vesicles and cancer multidrug resistance: undesirable Intercellular messengers?(Multidisciplinary Digital Publishing Institute (MDPI), 2023-07-27) Bucci Muñoz, María; Gola, Aldana Magalí; Rigalli, Juan Pablo; Ceballos Mancini, María Paula; Ruiz, María LauraÍtem Acceso Abierto Adaptive downregulation of Cl- /HCO3 - exchange activity in rat hepatocytes under experimental obstructive cholestasis(Public Library of Science (PLOS), 2019-02-21) Miszczuk, Gisel Sabrina; Banales, Jesus M.; Zucchetti, Andrés E.; Pisani, Gerardo Bruno; Boaglio, Andrea C.; Saez, Elena; Medina, Juan F.; Roma, Marcelo Gabriel; Crocenzi, Fernando A.Ítem Acceso Abierto Aquaporin membrane channels in oxidative stress, cell signaling, and aging: recent advances and research trends(Hindawi, 2018-03-27) Tamma, Grazia; Valenti, Giovanna; Grossini, Elena; Donnini, Sandra; Marino, Angela; Marinelli, Raúl A.; Calamita, GiuseppeÍtem Acceso Abierto Hepatocyte and sertoli cell aquaporins, recent advances and research trends(MDPI, 2016-07-09) Bernardino, Raquel L.; Marinelli, Raúl A.; Maggio, Anna; Gena, Patrizia; Cataldo, Ilaria; Alves, Marco G.; Svelto, María; Oliveira, Pedro F.; Calamita, GiuseppeÍtem Acceso Abierto Aquaporins as targets of dietary bioactive phytocompounds(Frontiers Media, 2018-04-18) Tesse, Angela; Grossini, Elena; Tamma, Grazia; Brenner, Catherine; Portincasa, Piero; Marinelli, Raúl A.; Calamita, GiuseppeÍtem Acceso Abierto Sexual dimorphism of adipose and hepatic aquaglyceroporins in health and metabolic disorders(Frontiers Media, 2015-11-05) Rodríguez, Amaia; Marinelli, Raúl A.; Tesse, Angela; Frühbeck, Gema; Calamita, GiuseppeÍtem Acceso Abierto Data of H2O2 release from AQP8-knockdown rat hepatocyte mitochondria(Elsevier, 2019-03-06) Danielli, Mauro; Marrone, Julieta; Capiglioni, Alejo M.; Marinelli, Raúl A.Ítem Acceso Abierto Attenuation of liver cancer development by oral glycerol supplementation in the rat(Springer, 2017-03-02) Capiglioni, Alejo M.; Lorenzetti, Florencia; Quiroga, Ariel Darío; Parody, Juan Pablo; Ronco, María Teresa; Pisani, Gerardo Bruno; Carrillo, María Cristina; Ceballos Mancini, María Paula; Alvarez, María de Luján; Rassetto, Mauricio: asistencia técnicaÍtem Acceso Abierto Quercetin prevents liver carcinogenesis by inducing cell cycle arrest, decreasing cell proliferation and enhancing apoptosis(Wiley, 2014-02-03) Casella, María Laura; Parody, Juan Pablo; Ceballos Mancini, María Paula; Quiroga, Ariel Darío; Ronco, María Teresa; Francés, Daniel Eleazar; Monti, Juan Alberto; Pisani, Gerardo Bruno; Carnovale, Cristina Ester; Carrillo, María Cristina; Alvarez, María de Luján