The Na<sup>+</sup>/H<sup>+</sup>exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation

Bachmann, Oliver; Riederer, Brigitte; Rossmann, Heidi; Groos, Stephanie; Schultheis, Patrick J.; Shull, Gary E.; Gregor, Michael; Manns, Michael P.; Seidler, Ursula

doi:10.1152/ajpgi.00332.2003

Cited by 78 publications

(139 citation statements)

References 39 publications

Supporting

Mentioning

137

Contrasting

Order By: Relevance

“…Ultimately, despite significant expression and activity in both bowel and kidney, it appears that the absence of NHE2 can be compensated for. It is likely that NHE3 and NHE8 perform these compensatory roles, at least under some circumstances [6,51,69]. Perhaps not surprising, given the relatively benign phenotype for NHE2 KO mice, there is no known human disease ascribed to defects in this transporter [110].…”

Section: Slc9a2 -Nhe2mentioning

confidence: 99%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

141

125

View full text Add to dashboard Cite

The SLC9 gene family encodes Na + /H + exchangers (NHEs). These transmembrane proteins transport ions across lipid bilayers in a diverse array of species from prokaryotes to eukaryotes, including plants, fungi and animals. They utilize the electrochemical gradient of one ion to transport another ion against its electrochemical gradient. Currently, 13 evolutionarily conserved NHE isoforms are known in mammals [46,22,128]. The SLC9 gene family (solute carrier classification of transporters:www.bioparadigms.org) is divided into three subgroups [46]. The SLC9A subgroup encompasses plasmalemmal isoforms NHE1-5 (SLC9A1-5) and the predominantly intracellular isoforms NHE6-9 (SLC9A6-9). The SLC9B subgroup consists of two recently cloned isoforms, NHA1 and NHA2 (SLC9B1 and SLC9B2, respectively). The SLC9C subgroup consist of a sperm specific plasmalemmal NHE (SLC9C1) and a putative NHE, SLC9C2, for which there is currently no functional data [46].NHEs participate in the regulation of cytosolic and organellar pH as well as cell volume. In the intestine and kidney, NHEs are critical for transepithelial movement of Na + and HCO 3 -and thus for whole body volume and acid-base homeostasis [46]. Mutations in the NHE6 or NHE9 genes cause neurological disease in humans and are currently the only NHEs directly linked to human disease.However, it is becoming increasingly apparent that members of this gene family contribute to the pathophysiology of multiple human diseases.

show abstract

Section: Slc9a2 -Nhe2mentioning

confidence: 99%

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Fuster

Alexander

2013

Pflugers Arch - Eur J Physiol

141

125

View full text Add to dashboard Cite

show abstract

“…The activities of the different NHE isoforms are extracted by using the isoform selective NHE inhibitor HOE-642. The isoform selectivity of HOE-642 is dose-dependent, 1µM HOE642 inhibits NHE1 whereas 50µM HOE642 inhibits both NHE1 and 2 but not NHE3 [2,6]. The activities (A) of NHE isoforms can be calculated from the recoveries (R) as follows: …”

Section: Measurement Of Nhe Activitiesmentioning

confidence: 99%

Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

Pallagi-Kunstár

Farkas

Maléth

et al. 2014

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

Abstract:Bile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhea. In this study our aim was to characterise the cellular pathomechanism of bile-induced diarrhea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileumresected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na+/H+ exchanger (NHE) and Cl-/HCO3-exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhea, compared to control patients. Acute treatment of colonic crypts with 0.3mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 3 AbstractBile acids play important physiological role in the solubilisation and absorption of dietary lipids. However, under pathophysiological conditions, such as short bowel syndrome, they can reach the colon in high concentrations inducing diarrhea. In this study our aim was to characterise the cellular pathomechanism of bile-induced diarrhea using human samples. Colonic crypts were isolated from biopsies of patients (controls with negative colonoscopic findings) and of cholecystectomised/ileum-resected patients with or without diarrhoea. In vitro measurement of the transporter activities revealed impaired Na + /H + exchanger (NHE) and Cl -/HCO 3 -exchanger (CBE) activities in cholecystectomised/ileum-resected patients suffering from diarrhea, compared to control patients. Acute treatment of colonic crypts with 0.3mM chenodeoxycholate caused dose-dependent intracellular acidosis; moreover, the activities of acid/base transporters (NHE and CBE) were strongly impaired. This concentration of chenodeoxycholate did not cause morphological changes in colonic epithelial cells, although significantly reduced the intracellular ATP level, decreased mitochondrial transmembrane potential and caused sustained intracellular Ca 2+ elevation. We also showed that chenodeoxycholate induced Ca 2+ release from the endoplasmic reticulum and extracellular Ca 2+ influx contributing to the Ca 2+ elevation. Importantly, our results suggest that the chenodeoxycholate induced inhibition of NHE activities was ATP-dependent, whereas the inhibition of CBE activity was mediated by the sustained Ca 2+ elevation.We suggest that bile acids inhibit the function of ion transporters via cellular energy breakdown and Ca 2+ overload in human colonic epithelial cells, which can reduce fluid and electrolyte absorption in the colon and promote ...

show abstract

“…NHE2 and NHE3 play a major role in sodium and water absorption in the colon (4,42,54), whereas PepT1 is involved in ditripeptide uptake (mainly in the small intestine) (1). These genes were of particular interest because it has been proposed that NHE2, NHE3, and PepT1 were overexpressed after a resection in animal models and in humans (34,55).…”

Section: Nhe3 Nhe2 and Pept1 In The Colon Of Patients With Sbs And mentioning

confidence: 99%

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Joly¹,

Mayeur²,

Messing³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

, although a remaining colon improves patient outcome, there is no direct evidence of a mucosal colonic adaptation in humans. This prospective study evaluates morphology, proliferation status, and transporter expression level in the epithelium of the remaining colon of adult patients compared with controls. The targeted transporters were Na ϩ /H ϩ exchangers (NHE2 and 3) and oligopeptide transporter (PepT1). Twelve adult patients with a jejuno-colonic anastomosis were studied at least 2 yr after the last surgery and compared with 11 healthy controls. The depth of crypts and number of epithelial cells per crypt were quantified. The proliferating and apoptotic cell contents were evaluated by revealing Ki67, PCNA, and caspase-3. NHE2, NHE3, PepT1 mRNAs, and PepT1 protein were quantified by quantitative RT-PCR and Western blot, respectively. In patients with SBS compared with controls, 1) hyperphagia and severe malabsorption were documented, 2) crypt depth and number of cells per crypt were 35% and 22% higher, respectively (P Ͻ 0.005), whereas the proliferation and apoptotic levels per crypt were unchanged, and 3) NHE2 mRNA was unmodified; NHE3 mRNA was downregulated near the anastomosis and unmodified distally, and PepT1 mRNA and protein were unmodified. We concluded that, in hyperphagic patients with SBS with severe malabsorption, adaptive colonic changes include an increased absorptive surface with an unchanged proliferative/apoptotic ratio and well-preserved absorptive NHE2, NHE3, and PepT1 transporters. This is the first study showing a controlled nonpharmacological hyperplasia in the colon of patients with SBS.

show abstract

The Na⁺/H⁺exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation

Cited by 78 publications

References 39 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Contact Info

Product

Resources

About

The Na+/H+exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation

Cited by 78 publications

References 39 publications

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Traditional and emerging roles for the SLC9 Na+/H+ exchangers

Bile acids inhibit Na+/H+ exchanger and Cl−/HCO3 − exchanger activities via cellular energy breakdown and Ca2+ overload in human colonic crypts

Morphological adaptation with preserved proliferation/transporter content in the colon of patients with short bowel syndrome

Contact Info

Product

Resources

About

The Na⁺/H⁺exchanger isoform 2 is the predominant NHE isoform in murine colonic crypts and its lack causes NHE3 upregulation