首页> 外文期刊>American Journal of Physiology >Transcellular oxalate and Cl~-- absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate.
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Transcellular oxalate and Cl~-- absorption in mouse intestine is mediated by the DRA anion exchanger Slc26a3, and DRA deletion decreases urinary oxalate.

机译:DRA阴离子交换剂Slc26a3介导小鼠小肠中的跨细胞草酸盐和Cl〜-吸收,DRA缺失会减少尿中草酸盐的含量。

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Active transcellular oxalate transport in the mammalian intestine contributes to the homeostasis of this important lithogenic anion. Several members of the Slc26a gene family of anion exchangers have a measurable oxalate affinity and are expressed along the gut, apically and basolat-erally. Mouse Slc26a6 (PAT1) targets to the apical membrane of enterocytes in the small intestine, and its deletion results in net oxalate absorption and hyperoxaluria. Apical exchangers of the Slc26a family that mediate oxalate absorption have not been established, yet the Slc26a3 [downregulated in adenoma (DRA)] protein is a candidate mediator of oxalate uptake. We evaluated the role of DRA in intestinal oxalate and Cl~-- transport by comparing unidirectional and net ion fluxes across short-circuited segments of small (ileum) and large (cecum and distal colon) intestine from wild-type (WT) and DRA knockout (KO) mice. In WT mice, all segments demonstrated net oxalate and Cl~-- absorption to varying degrees. In KO mice, however, all segments exhibited net anion secretion, which was consistently, and solely, due to a significant reduction in the absorptive unidirectional fluxes. In KO mice, daily urinary oxalate excretion was reduced 66% compared with that in WT mice, while urinary creatinine excretion was unchanged. We conclude that DRA mediates a predominance of the apical uptake of oxalate and Cl~-- absorbed in the small and large intestine of mice under short-circuit conditions. The large reductions in urinary oxalate excretion underscore the importance of transcellular intestinal oxalate absorption, in general, and, more specifically, the importance of the DRA exchanger in oxalate homeostasis.
机译:活跃的跨细胞草酸盐在哺乳动物肠道中的转运有助于这种重要的石原性阴离子的体内稳态。阴离子交换剂的Slc26a基因家族的几个成员具有可测量的草酸酯亲和力,并沿肠胃,顶部和根部表达。小鼠Slc26a6(PAT1)靶向小肠中肠细胞的顶膜,其缺失导致草酸净吸收和高草酸尿症。尚未确定介导草酸盐吸收的Slc26a家族的顶端交换剂,但Slc26a3 [在腺瘤(DRA)中下调的蛋白]是草酸盐摄取的候选介体。我们通过比较野生型(WT)和DRA的小肠(回肠)和大肠(盲肠和远端结肠)的短路段上的单向离子流和净离子通量来评估DRA在肠草酸和Cl〜-转运中的作用敲除(KO)小鼠。在野生型小鼠中,所有节段均表现出不同程度的草酸和Cl-净吸收。然而,在KO小鼠中,所有片段均显示出净阴离子分泌,这是一致且唯一的,这是由于吸收性单向通量的显着降低。与野生型小鼠相比,KO小鼠的每日草酸尿排泄量减少了66%,而尿肌酐的排泄量却没有变化。我们得出的结论是,DRA介导了在短路条件下小鼠小肠和大肠中吸收的草酸盐和Cl〜-的顶端吸收。尿草酸盐排泄的大量减少强调了一般而言,跨细胞肠道草酸盐吸收的重要性,更具体地说,DRA交换剂在草酸盐体内平衡中的重要性。

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