Browsing by Author "Nervi, F"
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- ItemBiliary lipid secretion, bile acid metabolism, and gallstone formation are not impaired in hepatic lipase-deficient mice(W B SAUNDERS CO, 2003) Amigo, L; Mardones, P; Ferrada, C; Zanlungo, S; Nervi, F; Miquel, JF; Rigotti, AWhereas hepatic lipase (HL) has been implicated in lipoprotein metabolism and atherosclerosis, its role in controlling biliary lipid physiology has not been reported. This work characterizes plasma lipoprotein cholesterol, hepatic cholesterol content, bile acid metabolism, biliary cholesterol secretion, and gallstone formation in HL-deficient mice and C57BL/6 controls fed standard chow, a cholesterol-supplemented diet, or a lithogenic diet. Compared with C57BL/6 controls, HL knockout mice exhibited increased basal plasma high-density lipoprotein (HDL) cholesterol as well as reduced cholesterol levels transported in large lipoproteins in response to cholesterol-enriched diets. Hepatic cholesterol content and biliary cholesterol secretion of chow-fed HL knockout and wild-type mice were not different and increased similarly in both strains after feeding dietary cholesterol or a lithogenic diet. There were no differences in biliary bile acid secretion, bile acid pool size and composition, or fecal bile acid excretion between HL-deficient and control mice. HL knockout mice had a similar prevalence of gallstone formation as compared with control mice when both strains were fed with a lithogenic diet. In conclusion, the deficiency of HL has no major impact on the availability of lipoprotein-derived hepatic cholesterol for biliary secretion; HL expression is not essential for diet-induced gallstone formation in mice.
- ItemEnrichment of canalicular membrane with cholesterol and sphingomyelin prevents bile salt-induced hepatic damage(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 1999) Amigo, L; Mendoza, H; Zanlungo, S; Miquel, JF; Rigotti, A; Gonzalez, S; Nervi, FThese studies were undertaken to characterize the role of plasma membrane cholesterol in canalicular secretory functions and hepatocyte integrity against intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly increased in canalicular membranes of diosgenin-fed rats, suggesting a more resistant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas diosgenin-fed animals maintained bile flow, Maximal cholesterol output increased by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats, whereas bile salt output remained at control levels. The kinetics of glutamic oxalacetic: transaminase, lactic dehydrogenase, and alkaline phosphatase activities in bile showed a significantly faster release in control than in diosgenin-fed rats, After 30 min of hp travenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals.jlr Preservation of bile secretory functions and hepatocellular cytoprotection by diosgenin against the intravenous infusion of toxic doses of taurocholate was associated with an increased concentration of cholesterol and sphingomyelin in the canalicular membrane. The increase of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.
- ItemFibrates induce mdr2 gene expression and biliary phospholipid secretion in the mouse(PORTLAND PRESS LTD, 1996) Chianale, J; Vollrath, V; Wielandt, AM; Amigo, L; Rigotti, A; Nervi, F; Gonzalez, S; Andrade, L; Pizarro, M; Accatino, LDisruption of the murine mdr2 gene leads to the complete absence of biliary phospholipids. We tested the hypothesis that the increase in biliary phospholipid output induced by fibrates is mediated via induction of the hepatic mdr2 gene and its encoded product, the P-glycoprotein canalicular flippase. Increased levels of mdr2 mRNA were observed in the liver of mice treated with different fibrates: ciprofibrate, 660+/-155% (as compared with control group); clofibrate, 611+/-77 %; bezafibrate, 410+/-47 %; fenofibrate, 310+/-52 %; gemfibrozil, 190+/-25 % (P < 0.05 compared with control group). Induction of expression of the mdr gene family was specific to the mdr2 gene. Two- to three-fold increases in P-glycoprotein immunodetection were evident on the canalicular plasma-membrane domain of clofibrate- and ciprofibrate-treated mice. Biliary phospholipid output increased from 4.2+/-1.2 nmol/min per g of liver in the control group to 8.5+/-0.6, 7.1+/-2.9 and 5.8+/-2.5 in ciprofibrate-, clofibrate- and bezafibrate-treated mice respectively (P < 0.05 compared with control group). Moreover, a significant correlation between biliary phospholipid output and the relative levels of mdr2 mRNA was found (r = 0.86; P < 0.05). In treated animals, bile flow as well as cholesterol and bile acid outputs remained unchanged. Our findings constitute the first evidence that pharmacological modulation of biliary lipid secretion mediated by fibrates can be related to the overexpression of a specific liver gene product, the mdr2 P-glycoprotein, and are consistent with the hypothesis that the mdr2 P-glycoprotein isoform plays a crucial role in the secretion of biliary phospholipid.
- ItemGUTI: a new antigen in the Cromer blood group system(WILEY-BLACKWELL, 2003) Storry, JR; Sausais, L; Hue Roye, K; Mudiwa, F; Ferrer, Z; Blajchman, MA; Lublin, DM; Ma, BW; Miquel, JE; Nervi, F; Pereira, J; Reid, MEBACKGROUND: The Cromer blood group system consists of seven high-incidence and three low-incidence antigens carried on decay-accelerating factor (DAF). This report describes the identification and characterization of a new Cromer high-incidence antigen, named GUTI.
- ItemHepatic overexpression of sterol carrier protein-2 inhibits VLDL production and reciprocally enhances biliary lipid secretion(AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2003) Amigo, L; Zanlungo, S; Miquel, JF; Glick, JM; Hyogo, H; Cohen, DE; Rigotti, A; Nervi, FWe examined in vivo a role for sterol carrier protein-2 (SCP-2) in the regulation of lipid secretion across the hepatic sinusoidal and canalicular membranes. Recombinant adenovirus Ad.rSCP2 was used to overexpress SCP-2 in livers of mice. We determined plasma, hepatic, and biliary lipid concentrations; hepatic fatty acid (FA) and cholesterol synthesis; hepatic and biliary phosphatidylcholine (PC) molecular species; and VLDL triglyceride production. In Ad.rSCP2 mice, there was marked inhibition of hepatic fatty acids and cholesterol synthesis to <62% of control mice. Hepatic triglyceride contents were decreased, while cholesterol and phospholipids concentrations were elevated in Ad.rSCP2 mice. Hepatic VLDL triglyceride production fell in Ad.rSCP2 mice to 39% of control values. As expected, biliary cholesterol, phospholipids, bile acids outputs, and biliary PC hydrophobic index were significantly increased in Ad.rSCP2 mice. These studies indicate that SCP-2 overexpression in the liver markedly inhibits lipid synthesis as well as VLDL production, and alters hepatic lipid contents. In contrast, SCP-2 increased biliary lipid secretion and the proportion of hydrophobic PC molecular species in bile. These effects suggest a key regulatory role for SCP-2 in hepatic lipid metabolism and the existence of a reciprocal relationship between the fluxes of lipids across the sinusoidal and canalicular membranes.
- ItemMitochondrial DNA polymorphisms in Chilean aboriginal populations: Implications for the peopling of the southern cone of the continent(WILEY, 2000) Moraga, ML; Rocco, P; Miquel, JF; Nervi, F; Llop, E; Chakraborty, R; Rothhammer, F; Carvallo, PThe mitochondrial DNAs (mtDNAs) from individuals belonging to three Chilean tribes, the Mapuche, the Pehuenche, and the Yaghan, were studied both by RFLP analysis and D-loop (control region) sequencing. RFLP analysis showed that 3 individuals (1.3%) belonged to haplogroup A, 19 (8%) to haplogroup B, 102 (43%) to haplogroup C, and 113 (47.7%) to haplogroup D. Among the 73 individuals analyzed by D-loop sequencing we observed 37 different haplotypes defined by 52 polymorphic sites. Joint analysis of data obtained by RFLP and sequencing methods demonstrated that, regardless of the method of analysis, the mtDNA haplotypes of these three contemporary South American aborigine groups clustered into four main haplogroups, in a way similar to those previously described for other Amerindians. These results further revealed the absence of haplogroup A in both the Mapuche and Yaghan as well as the absence of haplogroup B in the Yaghan. These results suggest that the people of Tierra del Fuego are related to tribes from south-central South America. (C) 2000 Wiley-Liss, Inc.
- ItemSterol carrier protein 2 gene transfer changes lipid metabolism and enterohepatic sterol circulation in mice(W B SAUNDERS CO, 2000) Zanlungo, S; Amigo, L; Mendoza, H; Miquel, JF; Vio, C; Glick, JM; Rodriguez, A; Kozarsky, K; Quinones, V; Rigotti, A; Nervi, FBackground & Aims: Sterol carrier protein 2 (SCP-2) enhances sterol cycling and facilitates cholesterol translocation between intracellular organelles and plasma membrane in cultured cells, including hepatocytes. We examined the role of SCP-2 in hepatic cholesterol and lipid trafficking through the sinusoidal and canalicular secretory pathways of the liver in vivo. Methods: Recombinant adenovirus-mediated SCP-2 gene transfer was used to obtain hepatic overexpression of SCP-2 in C57BL/6 mice. Results: SCP-2 overexpression in the mouse liver resulted in an 8-fold increase of SCP-2 protein levels and determined various effects on lipid metabolism. It decreased high-density lipoprotein cholesterol and increased low-density lipoprotein (LDL) cholesterol concentrations. The expressions of hepatic LDL receptor, apolipoprotein (apo) A-I, apoB, and apoE were decreased. SCP-2 overexpression also increased hepatic cholesterol concentration, associated with decreased cholesterol neosynthesis. Increased biliary cholesterol and bile acid secretion, bile acid pool size, and intestinal cholesterol absorption were also observed. Conclusions: These results indicate that modulation of SCP-2 expression in the liver determines important modifications on lipoprotein metabolism, hepatic cholesterol synthesis and storage, biliary lipid secretion, bile acid metabolism and intestinal cholesterol absorption.
- ItemUptake of dodecanedioic acid by isolated rat liver(ELSEVIER SCIENCE BV, 1997) Greco, AV; Mingrone, G; DeGaetano, A; Amigo, L; Puglielli, L; Castagneto, M; Nervi, FThe uptake of dodecanedioic acid (C12), a dicarboxylic acid with 12 carbon atoms, was studied in the isolated perfused rat liver. Fifty pmol of C12 were injected as a bolus into the perfusing liver solution. The concentration of C12 in perfusate samples taken over 2 h from the beginning bf the experiments were analyzed by high performance liquid chromatography. An in vitro experimental session was performed to determine the binding curve of C12 to defatted bovine serum albumin. These data were then used to compute the perfusate C12 free fraction. The number of binding sites on the albumin molecule was equal to 4.29 +/- 0.21 (S.E.), while the affinity constant was 6.33 +/- 0.87 x 10(3) M(-1). Experimental values of perfusate C12 concentration versus time were individually plotted and fitted to a monoexponential decay for each liver perfused. The predicted C12 concentration at time zero averaged 0.354 +/- 0.0375 mu mol/ml. From this value the apparent volume of distribution of C12 was obtained and corresponded to 153.02 +/- 14.56 mi. The disappearance rate constant from the perfusate was 0.0278 +/- 0.0030 min(-1). The C12 half life was 26.6 +/- 2.3 min. The mean hepatic clearance from the perfusate was 4.08 +/- 0.38 ml/min. In conclusion, C12 is quickly taken up by the liver so that in about 100 min it was completely cleared from the perfusate. (C) 1997 Elsevier Science B.V.