Abstract

Urinary acidification is needed for normal acid-base homeostasis, and disorders of acidification are important causes of morbidity in chronic renal failure and other kidney diseases. The long term objectives of this proposal are to examine mechanisms for regulation of the renal proton pump at several levels of control.
The specific aims are: 1) To determine the primary structure of subunits from the bovine kidney proton pump. 2) To use bovine kidney proton pump DNA probes to identify classes of proton pump mRNAs in the rat kidney, and evaluate their functional significance. 3) To examine factors that affect kidney proton pump mRNAs in cultured cells. 4) To examine the genomic structure of the rat kidney proton pump. 5) To generate monoclonal antibodies to extracellular domains of the renal proton pump for studying its surface density. 6) To examine the possible role of cytosolic proteins in regulating proton pump enzymatic activity. These studies will enhance our understanding of how urinary acidification is regulated.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK038848-03
Application #
3238398
Study Section
General Medicine B Study Section (GMB)
Project Start
1986-12-01
Project End
1992-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
3
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Barnes-Jewish Hospital
Department
Type
DUNS #
City
Saint Louis
State
MO
Country
United States
Zip Code
63110

  Publications

Sautin, Yuri Y; Lu, Ming; Gaugler, Andrew et al. (2005) Phosphatidylinositol 3-kinase-mediated effects of glucose on vacuolar H+-ATPase assembly, translocation, and acidification of intracellular compartments in renal epithelial cells. Mol Cell Biol 25:575-89
Chen, Shih-Hua; Bubb, Michael R; Yarmola, Elena G et al. (2004) Vacuolar H+-ATPase binding to microfilaments: regulation in response to phosphatidylinositol 3-kinase activity and detailed characterization of the actin-binding site in subunit B. J Biol Chem 279:7988-98
Lu, Ming; Vergara, Sandra; Zhang, Li et al. (2002) The amino-terminal domain of the E subunit of vacuolar H(+)-ATPase (V-ATPase) interacts with the H subunit and is required for V-ATPase function. J Biol Chem 277:38409-15
Lu, M; Holliday, L S; Zhang, L et al. (2001) Interaction between aldolase and vacuolar H+-ATPase: evidence for direct coupling of glycolysis to the ATP-hydrolyzing proton pump. J Biol Chem 276:30407-13
Holliday, L S; Lu, M; Lee, B S et al. (2000) The amino-terminal domain of the B subunit of vacuolar H+-ATPase contains a filamentous actin binding site. J Biol Chem 275:32331-7
Lee, B S; Gluck, S L; Holliday, L S (1999) Interaction between vacuolar H(+)-ATPase and microfilaments during osteoclast activation. J Biol Chem 274:29164-71
Gluck, S L (1998) Acid-base. Lancet 352:474-9
Gluck, S L; Lee, B S; Wang, S P et al. (1998) Plasma membrane V-ATPases in proton-transporting cells of the mammalian kidney and osteoclast. Acta Physiol Scand Suppl 643:203-12
Holliday, L S; Dean, A D; Lin, R H et al. (1997) Low NO concentrations inhibit osteoclast formation in mouse marrow cultures by cGMP-dependent mechanism. Am J Physiol 272:F283-91
Lee, B S; Krits, I; Crane-Zelkovic, M K et al. (1997) A novel transcription factor regulates expression of the vacuolar H+-ATPase B2 subunit through AP-2 sites during monocytic differentiation. J Biol Chem 272:174-81

Showing the most recent 10 out of 39 publications