Rahmati N.,Erasmus University Rotterdam |
Kunzelmann K.,University of Regensburg |
Xu J.,University of Cincinnati |
Barone S.,University of Cincinnati |
And 6 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2013
SLC26A11 (human)/Slc26a11 (mouse), also known as kidney brain anion transporter (KBAT), is a member of the SLC26 anion transporter family and shows abundant mRNA expression in the brain. However, its exact cellular distribution and subcellular localization in the brain and its functional identity and possible physiological roles remain unknown. Expression and immunostaining studies demonstrated that Slc26a11 is abundantly expressed in the cerebellum, with a predominant expression in Purkinje cells. Lower expression levels were detected in hippocampus, olfactory bulb, cerebral cortex, and subcortical structures. Patch clamp studies in HEK293 cells transfected with mouse cDNA demonstrated that Slc26a11 can function as a chloride channel that is active under basal conditions and is not regulated by calcium, forskolin, or co-expression with cystic fibrosis transmembrane regulator. Single and double immunofluorescent labeling studies demonstrated the localization of vacuolar (V) H+-ATPase and Slc26a11 (KBAT) in the plasma membrane in Purkinje cells. Functional studies in HEK293 cells indicated that transfection with Slc26a11 stimulated acid transport via endogenous V H+-ATPase. We conclude that Slc26a11 (KBAT) is prominently distributed in output neurons of various subcortical and cortical structures in the central nervous system, with specific expression in Purkinje cells and that it may operate as a chloride channel regulating acid translocation by H+-ATPase across the plasma membrane and in intracellular compartments. © 2013 Springer-Verlag Berlin Heidelberg.
Pierre J.F.,Veterans Administration Research Services |
Pierre J.F.,University of Wisconsin - Madison |
Heneghan A.F.,Veterans Administration Research Services |
Heneghan A.F.,University of Wisconsin - Madison |
And 7 more authors.
Journal of Surgical Research | Year: 2013
Background: Parenteral nutrition (PN), with the lack of enteral feeding, compromises mucosal immune function and increases the risk of infections. We developed an ex vivo intestinal segment culture (EVISC) model to study the ex vivo effects of PN on susceptibility of the ileum to invasion by extra-intestinal pathogenic Escherichia coli (ExPEC) and on ileal secretion of antimicrobial secretory phospholipase A2 (sPLA2) in response to the pathogen. Materials and methods: Study 1: Using mouse (n = 7) ileal tissue, we examined the effects of ileal region (proximal versus distal) and varying ExPEC inoculum concentrations on ex vivo susceptibility to ExPEC invasion and sPLA2 secretion. Study 2: Ten mice were randomized to oral chow or intravenous PN feeding for 5 d (n = 5/group). Using the EVISC model, we compared the susceptibility of ileal tissue to invasion by ExPEC and sPLA2 secretion in response to the pathogen. Results: Study 1: The proximal ileum was more susceptible to invasion (P < 0.0001) and secreted lower amounts of sPLA2 (P = 0.0002) than the distal ileum. Study 2: Ileal tissue from PN-fed animals was more susceptible (approximately 4-fold, P = 0.018) to invasion than those from chow-fed animals. Ileal tissue from PN-fed animals secreted less sPLA2 (P < 0.02) than those from chow-fed animals. Conclusions: The data illustrate EVISC as a reproducible model for studying host-pathogen interactions and the effects of diet on susceptibility to infections. Specifically, the findings support our hypothesis that PN with the lack of enteral feeding decreases mucosal responsiveness to pathogen exposure and provides a plausible mechanism by which PN is associated with increased risk of infectious complication. © 2013 Elsevier Inc. All rights reserved.