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Your search keyword '"Roma, Marcelo G."' showing total 287 results
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287 results on '"Roma, Marcelo G."'

18. Cyproterone acetate induces a wide spectrum of acute liver damage including corticosteroid-responsive hepatitis: report of 22 cases

Author

Bessone, Fernando, Lucena, MI, Roma, Marcelo G., Stephens, Camilla, Medina-Cáliz, Inmaculada, Frider, Bernardo, Tsariktsian, Guillermo, Hernández, Nelia, Bruguera, Miquel, Gualano, Gisela, Fassio, Eduardo, Montero, Joaquín, Reggiardo, María V, Ferretti, Sebastián, Colombato, Luis, Tanno, Federico, Ferrer, Jaime, Zeno, Lelio, Tanno, Hugo, and Andrade, Raúl J.

Published
2016
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29. Disruption of function and localization of tight junctional structures and Mrp2 in sustained estradiol-17[beta]-D-glucuronide-induced cholestasis

Author

Mottino, Aldo D., Hoffman, Tim, Crocenzi, Fernando A., Sanchez Pozzi, Enrique J., Roma, Marcelo G., and Vore, Mary

Subjects
Cholestasis -- Research, Jaundice, Obstructive -- Research, Bile acid metabolism -- Research, Estradiol -- Research, Protein metabolism -- Research, Biological sciences
Abstract

Estradiol-17[beta]-D-glucuronide ([E.sub.2]17G) induces immediate and profound but transient cholestasis in rats when administered as a single bolus dose. Here, we examined the consequence of sustained [E.sub.2]17G cholestasis and assessed the function and localization of the tight junctional proteins zonula occludens-1 (ZO-1) and occludin and of the canalicular transporter multidrug resistance-associated protein-2 (Mrp2). An initial dose of [E.sub.2]17G (15 [micro]mol/kg iv) followed by five subsequent doses of 7.5 [micro]mol/kg from 60 to 240 min induced a sustained 40-70% decrease in bile flow. Following their biliary retrograde administration, cholera toxin B subunit-FITC or horseradish peroxidase were detected at the sinusoidal domain, indicating opening of the paracellular route; this occurred as early as 15 min after the first dose as well as 15 min after the last dose of [E.sub.2]17G, but not following the administration of vehicle in controls. Localization of ZO-1 and occludin was only slightly affected under acute cholestatic conditions but was severely disrupted under sustained cholestasis, with their appearance suggesting a fragmented structure. Endocytic internalization of Mrp2 to the pericanalicular region was apparent 20 rain after a single [E.sub.2]17G administration; however, Mrp2 was found more deeply internalized and partially redistributed to the basolateral membrane under sustained cholestasis. In conclusion, acute [E.sub.2]17G-induced cholestasis increased permeability of the tight junction, while sustained cholestasis provoked a significant redistribution of ZO-1, occludin, and Mrp2 in addition to increased permeability of the tight junction. Altered tight junction integrity likely contributes to impaired bile secretion and may be causally related to changes in Mrp2 localization. bile secretion; endocytic compartment; estrogen; paracellular permeability doi:10.1152/ajpgi.00496.2006

Published
2007

31. Role of microtubules in estradiol-17[beta]-D-glucuronide-induced alteration of canalicular Mrp2 localization and activity

Author

Mottino, Aldo D., Crocenzi, Fernando A., Pozzi, Enrique J. Sanchez, Veggi, Luis M., Roma, Marcelo G., and Vore, Mary

Subjects
Bilirubin -- Research, Colchicine -- Research, Microtubules -- Research, Biological sciences
Abstract

Estradiol-17[beta]-D-glucuronide ([E.sub.2]-17G) induces a marked but reversible inhibition of bile flow in the rat together with endocytic retrieval of multidrug resistance-associated protein 2 (Mrp2) from the canalicular membrane to intracellular structures. We analyzed the effect of pretreatment (100 min) with the microtubule inhibitor colchicine or lumicholchicine, its inactive isomer (1 [micro]mol/kg iv), on changes in bile flow and localization and function of Mrp2 induced by [E.sub.2]-17G (15 [micro]mol/kg iv). Bile flow and biliary excretion of bilirubin, an endogenous Mrp2 substrate, were measured throughout, whereas Mrp2 localization was examined at 20 and 120 min after [E.sub.2]-17G by confocal immunofluorescence microscopy and Western analysis. Colchicine pretreatment alone did not affect bile flow or Mrp2 localization and activity over the short time scale examined (3-4 h). Administration of [E.sub.2]-17G to colchicine-pretreated rats induced a marked decrease (85%) in bile flow and biliary excretion of bilirubin as well as internalization of Mrp2 at 20 min. These alterations were of a similar magnitude as in rats pretreated with lumicolchicine followed by [E.sub.2]-17G. Bile flow and Mrp2 localization and activity were restored to control levels within 120 min of [E.sub.2]-17G in animals pretreated with lumicolchicine. In contrast, in colchicine-pretreated rats followed by [E.sub.2]-17G, bile flow and Mrp2 activity remained significantly inhibited by 60%, and confocal and Western studies revealed sustained internalization of Mrp2 120 min after [E.sub.2]-17G. We conclude that recovery from [E.sub.2]-17G cholestasis, associated with exocytic insertion of Mrp2 in the canalicular membrane, but not its initial [E.sub.2]-17G-induced endocytosis, is a microtubule-dependent process. bile secretion; endocytic compartment; colchicine; bilirubin

Published
2005

32. Estradiol-17[beta]-D-glucuronide induces endocytic internalization of Bsep in rats

Author

Crocenzi, Fernando A., Mottino, Aldo D., Cao, Jingsong, Veggi, Luis M., Pozzi, Enrique J. Sanchez, Vore, Mary, Coleman, Roger, and Roma, Marcelo G.

Subjects
Physiology -- Research, Biological sciences
Abstract

Endocytic internalization of the multi-drug resistance-associated protein 2 (Mrp2) was previously suggested to be involved in estradiol-17[beta]-D-glucuronide ([E.sub.2]17G)-induced cholestasis. Here we evaluated in the rat whether a similar phenomenon occurs with the bile salt export pump (Bsep) and the ability of DBcAMP to prevent it. [E.sub.2]17G (15 [micro]mol/kg iv) impaired bile salt (BS) output and induced Bsep internalization, as assessed by confocal microscopy and Western blotting. Neither cholestasis nor Bsep internalization occurred in [TR.sup.-] rats lacking Mrp2. DBcAMP (20 [micro]mol/kg iv) partially prevented the decrease in bile flow and BS output and substantially prevented [E.sub.2]17G-induced Bsep internalization. In hepatocyte couplets, [E.sub.2]17G (50 [micro]M) diminished canalicular accumulation of a fluorescent BS and decreased Bsep-associated fluorescence in the canalicular membrane; DBcAMP (10 [micro]M) fully prevented both effects. In conclusion, our results suggest that changes in Bsep localization are involved in [E.sub.2]17G-induced impairment of bile flow and BS transport and that DBcAMP prevents this effect by stimulating insertion of canalicular transporter-containing vesicles. Mrp2 is required for [E.sub.2]17G to induce its harmful effect. bile salt; cholestasis; dibutyryl-adenosine 3',5'-cyclic monophosphate; F-actin; [TR.sup.-] rats

Published
2003

50. Adaptive Downregulation of Cl-/HCO3- Exchange Activity in Rat Hepatocytes under Experimental Obstructive Cholestasis

Author

Medicina, Medikuntza, Miszczuk, Gisel S., Bañales Asurmendi, Jesús María, Zucchetti, Andrés E., Pisani, Gerardo B., Boaglio, Andrea C., Sáez, Elena, Medina, Juan F., Roma, Marcelo G., Crocenzi, Fernando A., Medicina, Medikuntza, Miszczuk, Gisel S., Bañales Asurmendi, Jesús María, Zucchetti, Andrés E., Pisani, Gerardo B., Boaglio, Andrea C., Sáez, Elena, Medina, Juan F., Roma, Marcelo G., and Crocenzi, Fernando A.

Abstract

In obstructive cholestasis, there is an integral adaptive response aimed to diminish the bile flow and minimize the injury of bile ducts caused by increased intraluminal pressure and harmful levels of bile salts and bilirrubin. Canalicular bicarbonate secretion, driven by the anion exchanger 2 (AE2), is an influential determinant of the canalicular bile salt-independent bile flow. In this work, we ascertained whether AE2 expression and/or activity is reduced in hepatocytes from rats with common bile duct ligation (BDL), as part of the adaptive response to cholestasis. After 4 days of BDL, we found that neither AE2 mRNA expression (measured by quantitative real-time PCR) nor total levels of AE2 protein (assessed by western blot) were modified in freshly isolated hepatocytes. However, BDL led to a decrease in the expression of AE2 protein in plasma membrane fraction as compared with SHAM control. Additionally, AE2 activity (J(OH)-, mmol/L/min), measured in primary cultured hepatocytes from BDL and SHAM rats, was decreased in the BDL group versus the control group (1.9 +/- 0.3 vs. 3.1 +/- 0.2, p<0.005). cAMP-stimulated AE2 activity, however, was not different between SHAM and BDL groups (3.7 +/- 0.3 vs. 3.5 +/- 0.3), suggesting that cAMP stimulated insertion into the canalicular membrane of AE2-containing intracellular vesicles, that had remained abnormally internalized after BDL. In conclusion, our results point to the existence of a novel adaptive mechanism in cholestasis aimed to reduce biliary pressure, in which AE2 internalization in hepatocytes might result in decreased canalicular HCO3- output and decreased bile flow.

Published
2019

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