(FBIOyF) Departamento de Ciencias Fisiológicas - Artículo de Revista
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Examinando (FBIOyF) Departamento de Ciencias Fisiológicas - Artículo de Revista por Autor "Capiglioni, Alejo M."
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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 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 Biliary elimination of cholesterol can be modulated by hepatocyte mitochondrial Aquaporin-8 in mice(Nature Research, 2026-02-06) Capitani, María Celeste; Capiglioni, Alejo M.; Marinelli, Raúl A.; Marrone, JulietaSterol regulatory element-binding protein (SREBP) transcription factors directly or indirectly regulate key genes involved in hepatic cholesterol homeostasis, including biliary elimination. The ATP-binding cassette transporter G5 (ABCG5), located in hepatocyte canalicular plasma membranes, strongly controls the excretion of unesterified cholesterol into bile. Recently, we demonstrated in cultured hepatocytes that mitochondrial aquaporin-8 (mtAQP8), a channel protein capable of conducting H2O2, is involved in SREBP-controlled cholesterol synthesis. In this study, we evaluated whether hepatic mtAQP8 participates in modulating the biliary elimination of cholesterol. Using C57BL/6 mice, we found that adenovirus-induced mtAQP8 knockdown significantly downregulated the expression of sterol regulatory element-binding protein-2 (SREBP-2) and, through liver X receptor (LXR), that of ABCG5, which in turn decreased biliary cholesterol excretion. In contrast, mice with adenovirusmediated mitochondrial human AQP8 (hAQP8) expression significantly increased the expressions of SREBP-2, LXR, and ABCG5 and, consequently, the biliary excretion of cholesterol. A mitochondrialtargeted antioxidant, which has been shown to quench mitochondrial H2O2 release, did not affect mitochondrial hAQP8 expression, but prevented upregulation of SREBP-2, ABCG5, and biliary cholesterol excretion. Our data further support the involvement of mtAQP8 in hepatic cholesterol metabolism, suggesting that it modulates biliary cholesterol elimination through ABCG5 gene expression.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 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 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.