{"id":1056,"date":"2017-02-01T10:03:45","date_gmt":"2017-02-01T10:03:45","guid":{"rendered":"http:\/\/biodigestor.net\/?p=1056"},"modified":"2017-02-01T10:03:45","modified_gmt":"2017-02-01T10:03:45","slug":"the-bicarbonate-transporter-nbce1-slc4a4-is-necessary-for-at-least-two","status":"publish","type":"post","link":"https:\/\/biodigestor.net\/?p=1056","title":{"rendered":"The bicarbonate transporter NBCe1 (SLC4A4) is necessary for at least two"},"content":{"rendered":"

The bicarbonate transporter NBCe1 (SLC4A4) is necessary for at least two components of the proximal tubule contribution to acid\u2010base homeostasis filtered bicarbonate reabsorption and ammonia metabolism. Dicoumarol necessary for normal NaDC\u20101 expression and NBCe1 deletion induces a novel citrate reabsorptive pathway. Second NBCe1 KO increased 2\u2010oxoglutarate excretion. This could not be attributed to the metabolic acidosis as experimental acidosis Dicoumarol<\/a> decreased excretion. Increased 2\u2010oxoglutarate excretion could not be explained by changes in plasma 2\u2010oxoglutarate levels Dicoumarol the glutaminase I or the glutaminase II generation pathways 2 metabolism its putative apical 2\u2010oxoglutarate transporter OAT10 or its basolateral transporter NaDC\u20103. In summary: (1) NBCe1 is necessary for normal proximal tubule Dicoumarol NaDC\u20101 expression; Dicoumarol (2) NBCe1 deletion results in stimulation of a novel citrate reabsorptive pathway; and (3) NBCe1 is necessary for normal 2\u2010oxoglutarate metabolism through mechanisms impartial of expression of known transport and metabolic pathways. refers to the numbers of animal studied. Results NBCe1 deletion and organic anion excretion Our first studies examined the effect of NBCe1 deletion on urinary organic anion excretion. Physique?1 summarizes the results. NBCe1 deletion was associated with a significant decrease in citrate excretion (WT 305 effects of NBCe1 deletion on citrate excretion. NBCe1 KO resulted in no detectable (ND) urinary citrate excretion. … Mice with NBCe1 deletion spontaneously develop metabolic acidosis (Gawenis et?al. 2007; Handlogten et?al. 2015) which alone can alter organic anion metabolism. In order to determine the impartial effects of metabolic acidosis on organic anion excretion we examined urine from adult wild\u2010type mice1 with experimentally induced metabolic acidosis. Physique?1 summarizes these results. In wild\u2010type mice metabolic acidosis decreased both citrate (control 46.6 figure shows that NBCe1 deletion decreased NaDC\u20101 mRNA expression significantly. shows that experimental metabolic acidosis examined in adult wild\u2010type mice … Physique 3 NaDC\u20101 immunolabel in wild\u2010type and NBCe1 knock\u2010out pup kidneys. show characterization of NaDC\u20101 antibody used in these studies. IFN-alphaA<\/a> shows that apical immunolabel is present in proximal tubule segments … The effect of NBCe1 deletion on NaDC\u20101 expression cannot be explained by the associated metabolic acidosis. In wild\u2010type mice acid\u2010loading increased NaDC\u20101 mRNA expression (control 100 acidosis 164 shows effect of NBCe1 deletion on glutamine transaminase Dicoumarol K (GTK) expression and shows effect on shows expression of the basolateral organic anion transporter NaDC\u20103. NBCe1 KO decreased NaDC\u20103 expression significantly. Experimental metabolic acidosis … The specific mechanism of 2\u2010oxoglutarate secretion remains unclear but recent studies suggest the organic anion transporter OAT10 may mediate proximal tubule apical 2\u2010oxoglutarate secretion (Bahn et?al. 2008; Grimm et?al. 2015). As shown in Physique?6 NBCe1 KO was associated with a small but statistically significant decrease in OAT10 expression as compared to wild\u2010type littermates (WT 100 KO 81 show effect of NBCe1 deletion on Oxgr1 expression. NBCe1 KO did not alter Oxgr1 expression significantly. show that experimental metabolic acidosis … NBCe1 deletion and pendrin expression The 2\u2010oxoglutarate receptor Oxgr1 is usually expressed in pendrin\u2010positive collecting duct cells. Luminal 2\u2010oxoglutarate is usually believed to increase renal alkali excretion by stimulating pendrin\u2010mediated bicarbonate secretion (Tokonami et?al. 2013). In mice with NBCe1 deletion pendrin protein expression quantified by immunoblot analysis was decreased significantly (Fig.?8). The absence of significant urine alkalinization in NBCe1 KO mice appears to be due at least in part to decreased expression of the 2\u2010oxoglutarate target protein pendrin. Physique 8 NBCe1 deletion alters pendrin protein expression. shows immunoblot assay for pendrin in wild\u2010type and NBCe1 KO pup kidneys. shows quantification of immunoblot analysis. NBCe1 deletion decreased pendrin protein expression … Discussion These studies provide the first examination of NBCe1’s role in renal organic anion metabolism. NBCe1 deletion decreased urinary citrate excretion comparable to that expected from the.<\/p>\n","protected":false},"excerpt":{"rendered":"

The bicarbonate transporter NBCe1 (SLC4A4) is necessary for at least two components of the proximal tubule contribution to acid\u2010base homeostasis filtered bicarbonate reabsorption and ammonia metabolism. Dicoumarol necessary for normal NaDC\u20101 expression and NBCe1 deletion induces a novel citrate reabsorptive pathway. Second NBCe1 KO increased 2\u2010oxoglutarate excretion. This could not be attributed to the metabolic… Continue reading The bicarbonate transporter NBCe1 (SLC4A4) is necessary for at least two<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[34],"tags":[996,997],"class_list":["post-1056","post","type-post","status-publish","format-standard","hentry","category-acid-sensing-ion-channel-3","tag-dicoumarol","tag-ifn-alphaa","entry"],"_links":{"self":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/1056"}],"collection":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=1056"}],"version-history":[{"count":1,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/1056\/revisions"}],"predecessor-version":[{"id":1057,"href":"https:\/\/biodigestor.net\/index.php?rest_route=\/wp\/v2\/posts\/1056\/revisions\/1057"}],"wp:attachment":[{"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=1056"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=1056"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/biodigestor.net\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=1056"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}