Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis.
Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis.
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DOI：
10.1002/cphy.c170014
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发表时间：
2017-12-12
影响因子：
5.8
通讯作者：
Ganapathy V
中科院分区：
文献类型：
--
作者：
Sivaprakasam S;Bhutia YD;Yang S;Ganapathy V
短链脂肪酸（SCFA；乙酸盐、丙酸盐和丁酸盐）是通过膳食纤维的细菌发酵在结肠中产生的。虽然质子化形式的扩散是一条重要途径，但载体介导的机制构成了阴离子形式 SCFA 进入结肠上皮的主要途径。多种转运系统在细胞摄取 SCFA 的过程中发挥作用。 MCT1 (SLC16A1) 和 MCT4 (SLC16A3) 是 H+ 耦合的，介导 SCFA 的电中性转运（H+: SCFA 化学计量；1:1）。 MCT1 在结肠上皮的顶膜和基底外侧膜中表达，而 MCT4 在基底外侧膜中特异性表达。 SMCT1 (SLC5A8) 和 SMCT2 (SLC5A12) 是 Na+ 耦合的； SMCT1 介导的运输是生电的（Na+: SCFA 化学计量；2:1），而 SMCT2 介导的运输是电中性的（Na+: SCFA 化学计量；1:1）。 SMCT1 和 SMCT2 仅在顶膜中表达。阴离子交换机制也在顶膜中起作用，其中阴离子形式的 SCFA 进入与碳酸氢根流出耦合；然而，这种交换剂的分子身份仍然未知。所有这些转运蛋白都受到监管，特别是它们的底物本身；该过程涉及以 SCFA 作为信号分子的细胞表面受体。这些转运蛋白在溃疡性结肠炎和结肠癌中的表达存在显着变化。肿瘤相关的变化是通过 p53 和 HIF1α 的转录调节以及启动子甲基化发生的。由于 SCFA 对于最佳结肠健康至关重要，因此负责结肠上皮中这些细菌产物的进入和跨细胞转移的转运蛋白是生理条件和疾病状态下结肠功能的关键决定因素。
Short-chain fatty acids (SCFA; acetate, propionate, and butyrate) are generated in colon by bacterial fermentation of dietary fiber. Though diffusion in protonated form is a significant route, carrier-mediated mechanisms constitute the major route for the entry of SCFA in their anionic form into colonic epithelium. Several transport systems operate in cellular uptake of SCFA. MCT1 (SLC16A1) and MCT4 (SLC16A3) are H+-coupled and mediate electroneutral transport of SCFA (H+: SCFA stoichiometry; 1:1). MCT1 is expressed both in the apical membrane and basolateral membrane of colonic epithelium whereas MCT4 specifically in the basolateral membrane. SMCT1 (SLC5A8) and SMCT2 (SLC5A12) are Na+-coupled; SMCT1-mediated transport is electrogenic (Na+: SCFA stoichiometry; 2:1) whereas SMCT2-mediated transport is electroneutral (Na+: SCFA stoichiometry; 1:1). SMCT1 and SMCT2 are expressed exclusively in the apical membrane. An anion-exchange mechanism also operates in the apical membrane in which SCFA entry in anionic form is coupled to bicarbonate efflux; the molecular identity of this exchanger however remains unknown. All these transporters are subject to regulation, notably by their substrates themselves; this process involves cell-surface receptors with SCFA as signaling molecules. There are significant alterations in the expression of these transporters in ulcerative colitis and colon cancer. The tumor-associated changes occur via transcriptional regulation by p53 and HIF1α and by promoter methylation. As SCFA are obligatory for optimal colonic health, the transporters responsible for the entry and transcellular transfer of these bacterial products in colonic epithelium are critical determinants of colonic function under physiological conditions and in disease states.
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DOI：
10.1177/0148607113486809
发表时间：
2013-11
期刊：
JPEN. Journal of parenteral and enteral nutrition
影响因子：
--
作者：
Cresci G;Nagy LE;Ganapathy V
通讯作者：
Ganapathy V
影响因子：
4.8
作者：
Brown, AJ;Goldsworthy, SM;Dowell, SJ
通讯作者：
Dowell, SJ
影响因子：
11.2
作者：
Doherty JR;Yang C;Scott KE;Cameron MD;Fallahi M;Li W;Hall MA;Amelio AL;Mishra JK;Li F;Tortosa M;Genau HM;Rounbehler RJ;Lu Y;Dang CV;Kumar KG;Butler AA;Bannister TD;Hooper AT;Unsal-Kacmaz K;Roush WR;Cleveland JL
通讯作者：
Cleveland JL
DOI：
10.1042/bj20121248
发表时间：
2013-02-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Coothankandaswamy V;Elangovan S;Singh N;Prasad PD;Thangaraju M;Ganapathy V
通讯作者：
Ganapathy V
影响因子：
--
作者：
Bhutia YD;Ogura J;Sivaprakasam S;Ganapathy V
通讯作者：
Ganapathy V