#EB2012: Renal Section Honors

Apr 24 2012 Published by under [Biology&Environment], EB2012 Meeting

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Di Feng makes an award-winning presentation

Every year the Renal Section of the American Physiological Society grants awards to undergraduate and post-doctoral trainees for work they submit and present at the meeting. A committee selects 5 finalists based on the abstract submitted, and their presentations are judged during the Posters and Professors Session that was held on Sunday, April 22.

Undergraduate Finalists

  • Justine Abais, Virginia Commonwealth University
  • Di Feng, Medical College of Wisconsin
  • Teresa Kennedy-Lydon, Roya Veterinary College
  • Jacob Richards, University of Floriday
  • Ryan Cornelius, University of Nebraska

The award went to Di Feng for her work :

Genetic regulation and functional relevance of the p67phox gene in salt-sensitive hypertension
Di Feng1, Chun Yang1, Jozef Lazar2, David Mattson1, Paul O'Connor1, Allen W. Cowley, Jr. 1,3. 1Physiology Department, 2Human and Molecular Genetics Center, 3Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI

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Feng receives her plaque while Jacob Richards looks on

A narrow region on rat Chr 13 was identified to harbor salt- sensitive genes. p67phox, a cytosolic subunit of NAD(P)H oxidase, is located in this region. We have previously found that on a high salt diet, the renal outer medulla (OM) of Dahl salt-sensitive (SS) rats exhibited higher levels of p67phox expression and NAD(P)H oxidase activity than salt-resistant congenic rats that contain the p67phox allele from the salt-resistant Brown Norway rat. We generated the first p67phox null mutant (p67phox-/-) SS rat in which we observed significantly reduced salt-sensitive hypertension. In our present study, we sequenced a 1650 bp promoter region and found that the SS allele of p67phox had a 204 bp deletion and four SNPs compared to the BN allele. The activity of the SS p67phox promoter was 1.7 fold higher than that of the BN p67phox promoter. We further characterized p67phox-/- rats and showed that they had a 40% reduction in OM H2O2 levels measured from interstitial fluid collected by microdialysis. Respiratory burst responses of peritoneal macrophages to phorbol 12-myristate 13-acetate were abolished in p67phox-/- rats. p67phox-/- rats also showed reduced renal injury, including reduced OM fibrosis, infiltrated T cells and macrophages, and glomerulosclerosis. These data provide new insights into the genetic regulation and functional relevance of p67phox in salt-sensitive hypertension. (HL-82798; HL-29587)

Postdoctoral finalists included:

  •  Krishna Boini, Virginia Commonwealth University
  • Richard Grimm, University of Mryland
  • Elena Mironova, University of Texas-San Antonio
  • Ann Riquier-Brison, University of Southern California
  • Ankita Roy, University of Pittsburgh
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Dr. Grimm gives me a guided tour of his work

Richard Grimm took home the award for this submission:

SPAK, OSR1 and Cab39/MO25 form an Interdependent Signaling system which Regulates Thiazide-Sensitive Salt- transport, Distal Tubule Mass and Blood Pressure
P Richard Grimm1, Tarvinder Taneja1, Jie Liu1, Richard Coleman1, Yang-Yi Chen1, Eric Delpire2, James B Wade1, Paul A Welling1. 1Physiology, University of Maryland School of Medicine, Baltimore, MD, 2Anesthesiology, Vanderbilt School of Medicine, Nashville, TN

STE20/SPS-1-related proline-alanine-rich protein kinase (SPAK) and, Oxidative Stress Related Kinase (OSR1), co-localize at the apical membrane of the Thick ascending Limb (TAL) and Distal Convoluted Tubule (DCT) and both regulate the potassium- dependent sodium-chloride co-transporter, NKCC2, thiazide- sensitive sodium-chloride cotransporter, NCC in vitro. Yet genetic ablation of SPAK in mice causes a salt-wasting nephropathy that is restricted to the DCT, reminiscent of Gitelman’s syndrome. Here, we explore why proper DCT function is especially SPAK- dependent. In the TAL of SPAK-/- mice, OSR1 and Cab39/MO25, a newly described OSR1/SPAK regulatory protein, remain at the apical membrane where they function with a compensatory increase in the AMP-activated kinase (AMPK) to hyper- phosphorylate NKCC2. By contrast, the OSR1/SPAK/M025 signal transduction apparatus is completely disrupted in the DCT. OSR1 and MO25 become largely displaced from the thiazide-sensitive sodium-chloride cotransporter, NCC, and the apical membrane. OSR1 redistributes to dense punctate structures within the cytoplasm. These changes are paralleled by a dramatic decrease in NCC abundance and phosphorylation. Without SPAK and the proper localization of OSR1 and MO25, phosphorylation- dependent regulation of NCC by dietary sodium restriction is lost. SPAK-/- mice also exhibit a decrease in the mass of the distal convoluted tubule, exclusive to DCT1. As a result of the interdependent nature of OSR1 and MO25 on SPAK in the DCT, SPAK-/- mice are highly sensitive to dietary salt-restriction, displaying prolonged negative sodium balance and hypotension.

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Dr. Grimm wins

 

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