D-Glucose Acts via Sodium/Glucose Cotransporter 1 to Increase NHE3 in Mouse Jejunal Brush Border by a Na plus/H plus Exchange Regulatory Factor 2-Dependent Process

被引：69

作者：

Lin, Rong ^{[1
,3
]}

Murtazina, Rakhilya ^{[1
]}

Cha, Boyoung ^{[1
]}

Chakraborty, Molee ^{[1
]}

Sarker, Rafiquel ^{[1
]}

Chen, Tian-E ^{[1
]}

Lin, Zhihong ^{[1
]}

Hogema, Boris M. ^{[4
]}

de Jonge, Hugo R. ^{[4
]}

Seidler, Ursula ^{[5
]}

Turner, Jerrold R. ^{[6
]}

Li, Xuhang ^{[1
]}

Kovbasnjuk, Olga ^{[1
]}

Donowitz, Mark ^{[1
,2
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Med, Div Gastroenterol, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21205 USA

[3] Huazhong Univ Sci & Technol, GI Div, Wuhan Union Hosp, Tongji Med Sch, Wuhan 430074, Peoples R China

[4] Erasmus Univ, Dept Biochem, Med Ctr, NL-3000 DR Rotterdam, Netherlands

[5] Hannover Med Sch, Dept Gastroenterol, D-3000 Hannover, Germany

[6] Univ Chicago, Dept Pathol, Chicago, IL 60637 USA

来源：

GASTROENTEROLOGY | 2011年 / 140卷 / 02期

基金：

美国国家卫生研究院;

关键词：

Intestinal Na Absorption; Cholera Toxin; Exocytosis; Ezrin; NHERF2; PROXIMAL TUBULE; INTESTINAL EPITHELIA; NA+/H+ EXCHANGER-3; OK CELLS; MEMBRANE; ACTIVATION; EZRIN; TRAFFICKING; MOBILITY; TRANSLOCATION;

D O I：

10.1053/j.gastro.2010.10.042

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

BACKGROUND & AIMS: Oral rehydration solutions reduce diarrhea-associated mortality. Stimulated sodium absorption by these solutions is mediated by the Na+/H+ hydrogen exchanger NHE3 and is increased by Na+-glucose co-transport in vitro, but the mechanisms of this up-regulated process are only partially understood. METHODS: Intracellular pH was measured in jejunal enterocytes of wild-type mice and mice with disrupted Na+/H+ exchange regulatory co-factor 2 (NHERF2-/- mice) by multiphoton microscopy. Diarrhea was induced by cholera toxin. Caco-2BBe cells that express NHE3 and the sodium/glucose cotransporter 1 (SGLT1) were studied by fluorometry, before and after siRNA-mediated knockdown of NHERF1 or NHERF2. NHE3 distribution was assessed by cell-surface biotinylation and confocal microscopy. Brush-border mobility was determined by fluorescence recovery after photobleaching and confocal microscopy. RESULTS: The nonmetabolized SGLT1 substrate alpha-methyl-D-Glu (alpha-MD-G) activated jejunal NHE3; this process required Akt and NHERF2. alpha-MD-G normalized NHE3 activity after cholera toxin-induced diarrhea. alpha-MD-G-stimulated jejunal NHE3 activity was defective in NHERF2-/- mice and cells with NHERF2 knockdown, but occurred normally with NHERF1 knockdown; was associated with increased NHE3 surface expression in Caco-2 cells, which also was NHERF2-dependent; was associated with dissociation of NHE3 from NHERF2 and an increase in the NHE3 mobile fraction from the brush border; and was accompanied by a NHERF2 ezrin-radixin-moesin-binding domain-dependent increase in co-precipitation of ezrin with NHE3. CONCLUSIONS: SGLT1-mediated Na-glucose cotransport stimulates NHE3 activity in vivo by an Akt- and NHERF2-dependent signaling pathway. It is associated with increased brush-border NHE3 and association between ezrin and NHE3. Activation of NHE3 corrects cholera toxin-induced defects in Na absorption and might contribute to the efficacy of oral rehydration solutions.

引用

页码：560 / 571

页数：12

共 1 条

[1] D-Glucose/SGLT1 Stimulates NHE3 Activity in Intact Mouse Jejunum, a Contributor to the Effect of Ors, By An AKT Dependent Process
Lin, Rong
Murtazina, Rakhilya
Kovbasnjuk, Olga
Sarker, Rafiquel
Cha, Boyoung
Zachos, Nicholas C.
Tse, Ming
Donowitz, Mark
GASTROENTEROLOGY, 2009, 136 (05) : A136 - A136

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