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TRAFFICKING OF SODIUM TRANSPORTERS AS A WAY OF CONTROLLING SODIUM HOMEOSTASIS
by
Monica Sandberg
A Dissertation Presented to the
FACULTY OF THE GRADUATE SCHOOL
UNIVERSITY OF SOUTHERN CALIFORNIA
In Partial Fulfillment of the
Requirements for the Degree
DOCTOR OF PHILOSOPHY
(PHYSIOLOGY & BIOPHYSICS)
May 2007
Copyright 2007 Monica Sandberg
Object Description
| Title | Trafficking of sodium transporters as a way of controlling sodium homeostasis |
| Author | Sandberg, Monica |
| Author email | msandber@usc.edu |
| Degree | Doctor of Philosophy |
| Document type | Dissertation |
| Degree program | Physiology & Biophysics |
| School | Keck School of Medicine |
| Date defended/completed | 2007-03-23 |
| Date submitted | 2007 |
| Restricted until | Unrestricted |
| Date published | 2007-04-23 |
| Advisor (committee chair) | McDonough, Alicia |
| Advisor (committee member) |
Hamm-Alvarez, Sarah [illegible] [illegible] |
| Abstract | Whole body sodium and volume homeostasis is controlled by the kidney. If volume is not corrected, a generalized vascular contraction occurs to normalize tissue blood flow resulting in hypertension. Na+ transport along the nephron can be regulated by altering: 1) total transporter abundance, 2) subcellular distribution of transporters or 3) activity/transporter. The aims of this dissertation were to determine: 1) whether trafficking is an important mechanism regulating sodium transporters in response to a high salt diet, 2) the time course of the molecular responses occurring in response to a high salt diet, 3) the importance of AngiotensinII in the trafficking of distal tuble NCC. High salt diet protocol: SD rats were fed a normal 0.4% NaCl diet (NS) diet for 3 wks then either remained on the NS diet or switched to a high salt 4% NaCl diet (HS) overnight or 3 weeks. Kidneys were excised and either fractionated on sorbitol density gradients or analyzed by confocal microscopy. Captopril protocol: SD rats were either infused with the ACE inhibitor captopril acutely (at 12 µg/min) for 20 minutes or infused for 20 min with captopril (12 µg/min) followed by 20 minutes of captopril (12 µg/min) and AngII (20 ng x kg-1 x min-1).; Results: HS diet decreased abundance of NCC but not NHE3, NaPi2, NKCC, ENaC- or sodium pump subunits. Overnight and 3 wks HS diet caused a significant redistribution of NCC, NHE3, NaPi2, NKCC2, and NHE3 associated proteins NHERF1, DPPIV and myosin VI from the apical enriched low density membrane fractions to higher density fractions. Retraction of NHE3 to the base of the microvilli during HS was evident by confocal microscopy, while changes in cellular distribution of NaPi2, DPPIV, MyosinVI and NHERF1 were not evident at this resolution suggesting only partial redistribution. Redistribution of NCC was confirmed by immunoelectron microscopy. We conclude that the molecular mechanisms the kidney uses to control sodium homeostasis in response to a HS diet include redistribution of PT NHE3 and TAL NKCC2 to higher density membranes, and internalization and decrease in abundance of DCT NCC. We also conclude that AngiotensinII is important for the trafficking of NCC. |
| Keyword | sodium homeostasis |
| Language | English |
| Part of collection | University of Southern California dissertations and theses |
| Publisher (of the original version) | University of Southern California |
| Place of publication (of the original version) | Los Angeles, California |
| Publisher (of the digital version) | University of Southern California. Libraries |
| Type | texts |
| Legacy record ID | usctheses-m448 |
| Rights | Sandberg, Monica |
| Repository name | Libraries, University of Southern California |
| Repository address | Los Angeles, California |
| Repository email | http://www.usc.edu/isd/libraries/services/ask_a_librarian/email/ |
| Filename | etd-Sandberg-20070423 |
| Archival file | uscthesesreloadpub_Volume51/etd-Sandberg-20070423.pdf |
Description
| Title | Page 1 |
| Full text | TRAFFICKING OF SODIUM TRANSPORTERS AS A WAY OF CONTROLLING SODIUM HOMEOSTASIS by Monica Sandberg A Dissertation Presented to the FACULTY OF THE GRADUATE SCHOOL UNIVERSITY OF SOUTHERN CALIFORNIA In Partial Fulfillment of the Requirements for the Degree DOCTOR OF PHILOSOPHY (PHYSIOLOGY & BIOPHYSICS) May 2007 Copyright 2007 Monica Sandberg |
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