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Ammonia detoxification via ureagenesis in rat hepatocytes involves mitochondrial aquaporin-8 channels
No full textHepatocyte mitochondrial ammonia detoxification via ureagenesis is critical for prevention of
hyperammonemia and hepatic encephalopathy. Aquaporin-8 (AQP8) channels facilitate the
membrane transport of ammonia. Since AQP8 is expressed in hepatocyte inner mitochondrial
membranes, we studied whether mitochondrial AQP8 (mtAQP8) plays a role in ureagenesis from
ammonia. Primary cultured rat hepatocytes were transfected with siRNAs targeting two different
regions of the rat AQP8 molecule or with scrambled control siRNA. After 48 h, the levels of
mtAQP8 protein specifically decreased by around 80% (P < 0.05) without affecting cell viability.
The mtAQP8-knockdown cells in the presence of ammonium chloride, showed a decrease in
ureagenesis of around 30% (P < 0.05). Glucagon strongly stimulated ureagenesis in control
hepatocytes (+120%, P < 0.05), whereas in mtAQP8-knockdown cells, it induced no significant
stimulation. Contrarily, mtAQP8-silencing induced no significant change in basal and glucagoninduced
ureagenesis when glutamine or alanine was used as source of nitrogen. NMR studies
using 15N-labeled ammonia, confirmed that glucagon-induced 15N-labeled urea synthesis was
markedly reduced in mtAQP8-knockdown hepatocytes (-90%, P < 0.05). In vivo studies in the
rat showed that under glucagon-induced ureagenesis, hepatic mtAQP8 protein expression was
markedly upregulated (+160% P < 0.05). Moreover, transport studies in liver inner mitochondrial
membrane vesicles showed that glucagon increased the diffusional permeability to the ammonia
analog [14C]methylamine (+80%, P < 0.05). Conclusion: Hepatocyte mtAQP8 channels
facilitate the mitochondrial uptake of ammonia and its metabolism into urea, mainly under
glucagon stimulation. This mechanism may be relevant to hepatic ammonia detoxification and in
turn, avoid the deleterious effects of hyperammonemia
Permeabilidad al amoníaco de la aquaporina-8 de rata (rAQP8) expresada en mitocondrias de levadura
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Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Lipopolysaccharide impairs hepatocyte ureagenesis from ammonia: involvement of mitochondrial aquaporin-8
No full textWe recently reported that hepatocyte mitochondrial aquaporin-8 (mtAQP8) channels
facilitate the uptake of ammonia and its metabolism into urea. Here we studied the
effect of bacterial lipopolysaccharides (LPS) on the ammonia-derived ureagenesis. In
LPS-treated rats, hepatic mtAQP8 protein expression and diffusional ammonia
permeability of liver inner mitochondrial
membranes were downregulated. NMR studies using 15N-labeled ammonia indicated
that basal and glucagon-induced ureagenesis from ammonia were significantly reduced
in hepatocytes from LPS-treated rats. Our data suggest that hepatocyte mtAQP8-
mediated ammonia removal via ureagenesis is impaired by LPS, a mechanism
potentially relevant to the molecular pathogenesis of defective hepatic ammonia
detoxification in sepsis
Altered expression and distribution of aquaporin-9 in the liver of rat with obstructive extrahepatic cholestasis
No full textRat hepatocytes express aquaporin-9 (AQP9), a basolateral channel permeable to water, glycerol, and other small neutral solutes. Although liver AQP9 is known for mediating the uptake of sinusoidal blood glycerol, its relevance in bile secretion physiology and pathophysiology remains elusive. Here, we evaluated whether defective expression of AQP9 is associated to secretory dysfunction of rat hepatocytes following bile duct ligation (BDL). By immunoblotting, 1-day BDL resulted in a slight decrease of AQP9 protein in basolateral membranes and a simultaneous increase of AQP9 in intracellular membranes. This pattern was steadily accentuated in the subsequent days of BDL since at 7 days BDL basolateral membrane AQP9 decreased by 85% whereas intracellular AQP9 increased by 115%. However, the AQP9 immunoreactivity of the total liver membranes from day 7 of BDL rats was reduced by 49% compared with the sham counterpart. Results were confirmed by immunofluorescence and immunogold electron microscopy and consistent with biophysical studies showing considerable decrease of the basolateral membrane water and glycerol permeabilities of cholestatic hepatocytes. The AQP9 mRNA was slightly reduced only at day 7 of BDL, indicating that the dysregulation was mainly occurring at a posttranslational level. The altered expression of liver AQP9 during BDL was not dependent on insulin, a hormone known to negatively regulate AQP9 at a transcriptional level, since insulinemia was unchanged in 7-day BDL rats. Overall, these results suggest that extrahepatic cholestasis leads to downregulation of AQP9 in the hepatocyte basolateral plasma membrane and dysregulated aquaporin channels contribute to bile flow dysfunction of cholestatic hepatocyte
Aquaporin-8-facilitated mitochondrial ammonia transport
No full textAquaporin-8 (AQP8) is a membrane channel permeable to water and ammonia. As AQP8 is expressed in the inner mitochondrial membrane of several mammalian tissues, we studied the effect of the AQP8 expression on the mitochondrial transport of ammonia. Recombinant rat AQP8 was expressed in the yeast Saccharomyces cerevisiae. The presence of AQP8 in the inner membrane of yeast mitochondria was demonstrated by subcellular fractionation and immunoblotting analysis. The ammonia transport was determined in isolated mitochondria by stopped flow light scattering using formamide as ammonia analog. We found that the presence of AQP8 increased by threefold mitochondrial formamide transport. AQP8-facilitated mitochondrial formamide transport in rat native tissue was confirmed in liver (a mitochondrial AQP8-expressing tissue) vs. brain (a mitochondrial AQP8 non-expressing tissue). Comparative studies indicated that the AQP8-mediated mitochondrial movement of formamide was markedly higher than that of water. Together, our data suggest that ammonia diffusional transport is a major function for mitochondrial AQP8
Liver Aquaporins: Significance in Canalicular and Ductal Bile Formation
No full textBile is primarily secreted in hepatocytes (i.e. the canalicular bile) and subsequently delivered to the intrahepatic bile ducts, where is modified by cholangiocytes (i.e. the ductal bile). Bile formation is the result of the coordinated interactions of membrane-transport systems that generate the vectorial movement of solutes and osmotically driven water molecules. Hepatocytes and cholangiocytes express aquaporins, specialized membrane channel proteins that facilitate the osmotic transport of water. In this review, we provide a summary of what is known on liver AQPs and their significance in canalicular and ductal bile formation under normal and pathological conditions
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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