Abstract

The catabolism of glutathione occurs through an inter-organ process which involves release from various tissues, transport via the plasma and hydrolysis which occurs primarily in the kidney. The kidney extracts 80-95% of the plasma glutathione in a single pass. Renal catabolism of glutathione is carried out by Gamma-glutamyltranspeptidase and either of two peptidase activities that are also associated with the lumenal surface of the renal brush border membrane. The rapid turnover of renal gluthathione involves its initial secretion from the proximal tubbule cells into the tubular lumen.
The specific aims of this proposal are to further characterize the hydrophobic domain of the Gamma-glutamyltranspeptidase, to determine the relative contribution of the two peptidase activities to the hydrolysis of cysteinylglycine, to characterize the mechanism of renal extraction of glutathione, to quantitate the process of glutathione secretion and to investigate the physiological function of the turnover of renal glutathione.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK026012-09
Application #
3227693
Study Section
General Medicine B Study Section (GMB)
Project Start
1979-12-01
Project End
1991-06-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
9
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Pittsburgh
Department
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213

  Publications

Joyce-Brady, M; Jean, J C; Hughey, R P (2001) gamma -glutamyltransferase and its isoform mediate an endoplasmic reticulum stress response. J Biol Chem 276:9468-77
Altschuler, Y; Kinlough, C L; Poland, P A et al. (2000) Clathrin-mediated endocytosis of MUC1 is modulated by its glycosylation state. Mol Biol Cell 11:819-31
Henkel, J R; Gibson, G A; Poland, P A et al. (2000) Influenza M2 proton channel activity selectively inhibits trans-Golgi network release of apical membrane and secreted proteins in polarized Madin-Darby canine kidney cells. J Cell Biol 148:495-504
Lavelle, J P; Negrete, H O; Poland, P A et al. (1997) Low permeabilities of MDCK cell monolayers: a model barrier epithelium. Am J Physiol 273:F67-75
Poland, P A; Kinlough, C L; Rokaw, M D et al. (1997) Differential glycosylation of MUC1 in tumors and transfected epithelial and lymphoblastoid cell lines. Glycoconj J 14:89-96
Joyce-Brady, M; Takahashi, Y; Oakes, S M et al. (1994) Synthesis and release of amphipathic gamma-glutamyl transferase by the pulmonary alveolar type 2 cell. Its redistribution throughout the gas exchange portion of the lung indicates a new role for surfactant. J Biol Chem 269:14219-26
Prezioso, J A; Hughey, R P; Wang, N et al. (1994) Gamma-glutamyltranspeptidase expression regulates the growth-inhibitory activity of the anti-tumor prodrug gamma-L-glutaminyl-4-hydroxy-3-iodobenzene. Int J Cancer 56:874-9
Scott, R D; Hughey, R P; Curthoys, N P (1993) Role of apical and basolateral secretion in turnover of glutathione in LLC-PK1 cells. Am J Physiol 265:F723-8
Altman, R A; Orr, A V; Lagenaur, C F et al. (1993) Expression of rat renal gamma-glutamyltranspeptidase in LLC-PK1 cells as a model for apical targeting. Biochemistry 32:3822-8