The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in vivo

Maher, M.; Jd, Gontarek; Bess, RS; Donowitz, Mark; Cj, Yeo

doi:10.1016/s0016-5085(97)70232-4

Cited by 66 publications

(43 citation statements)

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“…This observation is consistent with the previous report that Na + flux across the epithelia was decreased in the Vil2 KD/KD mouse ileum. 62) NHE3 contributes to basal ileal water and sodium absorption 63) and its function and cell surface expression seem to be regulated by ezrin. However, Hayashi et al reported that ezrin is not necessary for the apical localization, attachment to the cytoskeleton, baseline activity, and cAMP-induced phosphorylation of NHE3, but instead is required for cAMPmediated inhibition.…”

Section: Intestinesmentioning

confidence: 99%

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Kawaguchi

Yoshida

Hatano

et al. 2017

Biological & Pharmaceutical Bulletin

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Ezrin/radixin/moesin (ERM) proteins function as general cross-linkers between plasma membrane proteins and the actin cytoskeleton and are involved in the functional expression of membrane proteins on the cell surface. They also integrate Rho guanosine 5′-triphosphatase (GTPase) signaling to regulate cytoskeletal organization by sequestering Rho-related proteins. They act as protein kinase A (PKA)-anchoring proteins and sequester PKA close to its target proteins for their effective phosphorylation and functional regulation. Therefore, ERM proteins seem to play important roles in the membrane transport of electrolytes by ion channels and transporters. In this review, we focus on the pathophysiological roles of ERM proteins in in vivo studies and introduce the phenotypes of their knockout and knockdown mice.Key words ezrin/radixin/moesin protein; cytoskeleton; knockout mouse EZRIN/RADIXIN/MOESIN PROTEINS REGULATE CYTOSKELETAL ORGANIZATION BY CROSS-LINK-ING PLASMA MEMBRANES WITH THE ACTIN CY-TOSKELETON AND INTEGRATING RHO GTPASE SIGNALINGThe ezrin, radixin, and moesin (ERM) proteins are general cross-linkers between cortical actin filaments and plasma membranes. They are concentrated at cell surface structures such as microvilli, filopodia, uropods, ruffling membranes, retraction fibers, and cell adhesion sites where actin filaments are associated with plasma membranes, but not along cytoplasmic actin filaments such as stress fibers.1) ERM proteins also integrate Rho guanosine 5′-triphosphatase (GTPase) signaling to regulate cytoskeletal organization by sequestering Rhorelated proteins.2) The apparent molecular mass of ERM is 82, 80, and 75 kDa, respectively. They show high amino acid identity, especially in their amino-and carboxy-terminal domains. Their amino-terminal domains consisting of ca. 300 amino acid residues are termed "the band four point one and ERM (FERM) domain" because their amino acid sequences are conserved within ERM proteins and the erythrocyte band 4.1 protein (Fig. 1). FERM domains are also found in numerous membrane-associated signaling and cytoskeletal proteins such as talin.3) The FERM domains, which are composed of three structural modules (F1, F2, and F3), together form a compact clover-shaped structure 4,5) and bind to integral membrane proteins, [6][7][8][9][10][11][12][13][14][15][16] scaffold proteins, [17][18][19][20] and the Rho-related proteins (such as the Rho-guanosine 5′-diphosphate (GDP)-dissociation inhibitor [Rho-GDI] and Dbl) 21,22) listed in Table 1, as well as to phosphatidylinositol 4,5-bisphosphate (PIP 2 ). 12) The scaffold proteins Na + /H + exchanger regulatory factors (NHERF) 1 and 2, which contain two PDZ (PSD-95, Discs-large, and ZO-1) domains, bind to the FERM domain at the carboxy-terminus. 17,20) These PDZ domains on the NHERFs interact with the PDZ-binding motif of membrane proteins such as the cystic fibrosis transmembrane conductance regulator (CFTR) and Na 19,25,26) On the other hand, the carboxy-terminal domains, especially 34 amino acid residues, are also h...

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Section: Intestinesmentioning

confidence: 99%

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Kawaguchi

Yoshida

Hatano

et al. 2017

Biological & Pharmaceutical Bulletin

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“…3). NHE3, the predominant isoform mediating electroneutral Na ϩ absorption in the small intestine of most mammals (15,28,38), was initially assessed by treating the ischemia-injured porcine mucosa with the selective NHE3 inhibitor S-3226. This compound has a reported IC 50 for NHE3 of 0.2 M in porcine renal brush-border membrane vesicles (39).…”

Section: Blockade Of Apical Namentioning

confidence: 99%

Prostaglandin-mediated inhibition of Na⁺/H⁺exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

Moeser¹,

Nighot²,

Ryan³

et al. 2006

American Journal of Physiology-Gastrointestinal and Liver Physi

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. Prostaglandinmediated inhibition of Na ϩ /H ϩ exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine. Am J Physiol Gastrointest Liver Physiol 291: G885-G894, 2006. First published March 30, 2006 doi:10.1152/ajpgi.00380.2005.-Prostaglandins stimulate repair of the ischemia-injured intestinal barrier in the porcine ileum through a mechanism involving cAMP-dependent Cl Ϫ secretion and inhibition of electroneutral Na ϩ /H ϩ exchanger (NHE) activity. In the present study, we focused on the role of individual NHE isoforms in the recovery of barrier function. Ischemia-injured porcine ileal mucosa was mounted on Ussing chambers. Short-circuit current (Isc), transepithelial electrical resistance (TER), and isotopic fluxes of 22 Na were measured in response to PGE2 and selective inhibitors of epithelial NHE isoforms. Immunoassays were used to assess the expression of NHE isoforms. Forty-five minutes of intestinal ischemia resulted in a 45% reduction in TER (P Ͻ 0.01). Near-complete restitution occurred within 60 min. Inhibition of NHE2 with HOE-694 (25 M) added to the mucosal surface of the injured ileum stimulated significant elevations in TER, independent of changes in Isc and histological evidence of restitution. Pharmacological inhibition of NHE3 or NHE1 with mucosal S-3226 (20 M) or serosal cariporide (25 M), respectively, had no effect. Ischemiainjured tissues treated with mucosal S-3226 or HOE-694 exhibited equivalent reductions in mucosal-to-serosal fluxes of 22 Na ϩ (by ϳ35%) compared with nontreated ischemia-injured control tissues (P Ͻ 0.05). Intestinal ischemia resulted in increased expression of the cytoplasmic NHE regulatory factor EBP50 in NHE2 but not in NHE3 immunoprecipitates. Selective inhibition of NHE2, and not NHE3, induces recovery of barrier function in the ischemia-injured intestine.

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“…Since the preceding studies indicated that T cell activation does not produce an overt anion secretory response, we investigated the effect of anti-CD3 mAb treatment on Na + absorption across the jejunum. In the absence of nutrient solutes, sodium is absorbed in the small intestine primarily by the activity of luminal membrane Na + /H + exchangers, e.g., NHE3 and NHE2 (29,30). Therefore, changes in the magnitude of this process were investigated by measurement of isotopic Na + flux across intestine from control and anti-CD3 mAb-injected mice (3 hours after injection).…”

Section: Anti-cd3-induced Enteropoolingmentioning

confidence: 99%

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase

et al. 2002

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Inflammatory bowel disease (IBD) is associated with mucosal T cell activation and diarrhea. We found that T cell activation with anti-CD3 mAb induces profound diarrhea in mice. Diarrhea was quantified by intestinal weight-to-length (wt/l) ratios, mucosal Na+/K+-ATPase activity was determined and ion transport changes were measured in Ussing chambers. Anti-CD3 mAb increased jejunal wt/l ratios by more than 50% at 3 hours, returning to base line after 6 hours. Fluid accumulation was significantly reduced in TNF receptor-1 (TNFR-1–/–), but not IFN-γ knockout mice. Anti-CD3 mAb decreased mucosal Na+/K+-ATPase activity, which was blocked by anti-TNF mAb and occurred to a lesser degree in TNFR-1–/– mice. Neither α nor β subunits of Na+/K+-ATPase decreased in abundance at 3 hours. Intestinal tissue from anti-CD3–treated mice exhibited increased permeability to mannitol at 1 hour and decreases in electroneutral Na+ absorption, Na+-dependent glucose absorption, and cAMP-stimulated anion secretion at 3 hours. Furthermore, enteral fluid accumulation was observed in CFTR–/– mice, indicating a minor role of active anion secretion. These data suggest that diarrhea in IBD is due to TNF-mediated malabsorption rather than to secretory processes. T cell activation induces luminal fluid accumulation by increasing mucosal permeability and reducing epithelial Na+/K+-ATPase activity leading to decreased intestinal Na+ and water absorption

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The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in vivo

Cited by 66 publications

References 0 publications

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Prostaglandin-mediated inhibition of Na⁺/H⁺exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase

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The Na+/H+ exchange isoform NHE3 regulates basal canine ileal Na+ absorption in vivo

Cited by 66 publications

References 0 publications

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Pathophysiological Roles of Ezrin/Radixin/Moesin Proteins

Prostaglandin-mediated inhibition of Na+/H+exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine

T cell activation causes diarrhea by increasing intestinal permeability and inhibiting epithelial Na+/K+-ATPase

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Prostaglandin-mediated inhibition of Na⁺/H⁺exchanger isoform 2 stimulates recovery of barrier function in ischemia-injured intestine