The kidney plays an important role in the turnover of numerous peptides and proteins. Many studies have shown that proteins reabsorbed by endocytosis are eventually catabolized by lysosomes. Recently, we have shown that linear peptides of low-molecular weight are hydrolyzed by enzymes of the brush border of proximal tubules, prior to reabsorption. The long term goal of this research is to define the renal mechanisms for degradation and reabsorption of peptides and proteins. Studies will be directed at elucidating the cellular hydrolytic and transport proceses of luteninizing hormone releasing hormone, glucagon, insulin, growth hormone and lipoprotein. Experiments will be designed to determine the effect of molecular size, structure or composition and the effect of specific renal tubular injuries on the renal handling of these substances. This will be done by employing the techniques of tubular microperfusion in vivo and in vitro, incubation of peptides and proteins with isolated microvilli membranes from renal brush border, chromatographic and/or electrophoretic analyses of peptides, proteins, and hydrolytic products, and localization of transport events by electron microscopic autoradiography. Elucidation of renal mechanisms for handling proteins and peptides is essential in understanding the kidney's role in conserving amino acids and regulation of the effective serum level of peptide and protein hormones.

Project Start
1979-06-15
Project End
1987-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
15
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Type
School of Medicine & Dentistry
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611
Shimomura, A; Carone, F A; Peterson, D R (1988) Contraluminal uptake of serine in the proximal nephron. Biochim Biophys Acta 939:52-6
Carone, F A; Christensen, E I; Flouret, G (1987) Degradation and transport of AVP by proximal tubule. Am J Physiol 253:F1120-8
Flouret, G; Majewski, T; Peterson, D R et al. (1987) Effects of D-amino acid substituents on degradation of LHRH analogues by proximal tubule. Am J Physiol 252:E320-6
Carone, F A; Stetler-Stevenson, M A; May, V et al. (1987) Differences between in vitro and in vivo degradation of LHRH by rat brain and other organs. Am J Physiol 253:E317-21
Carone, F A; Nakamura, S; Goldman, B (1985) Urinary loss of glucose, phosphate, and protein by diffusion into proximal straight tubules injured by D-serine and maleic acid. Lab Invest 52:605-10