This investigation is interested in exploring how a single essential amino acid, specifically L-tryptophan, affects protein metabolism in the liver. In earlier reports from our laboratory we have described that L-tryptophan rapidly stimulates hepatic polyribosomal aggregation and protein synthesis. This effect appears to be related to alterations in both transcriptional and posttranscriptional controls. Our present proposal plans to explore at the cellular and subcellular levels how L-tryptophan may act, possibly directly on the nucleus (nuclear membrane), to stimulate enhanced nucleocytoplasmic translocation of mRNA. We plan to study in detail how proteins of the cytosol and nuclear membranes of the livers of tryptophan-treated rats are involved in the increased nucleocytoplasmic translocation of mRNA. In view of our recent findings that there are specific tryptophan binding sites on the nuclear envelopes of rat liver, we are now exploring the possible significance of the binding in relation to the enhanced nuclear RNA release in the liver due to tryptophan. We plan to characterize the structure and properties of the nuclear envelope tryptophan binding protein(s). Also we plan to determine whether the tryptophan specific binding may be affected by changes in the liver, such as induced by pretreatment of animals with a variety of hepatotoxic agents. Such information may offer basic insight as to how an important dietary component, as exemplified by L-tryptophan, may play a regulatory role in mammalian liver protein metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027339-08
Application #
3228253
Study Section
Metabolic Pathology Study Section (MEP)
Project Start
1980-09-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1989-06-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
George Washington University
Department
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052
Cosgrove, J W; Verney, E; Schwartz, A M et al. (1992) Tryptophan binding to nuclei of rat brain. Exp Mol Pathol 57:180-92
Sidransky, H; Verney, E; Cosgrove, J W et al. (1992) Studies with compounds that compete with tryptophan binding to rat hepatic nuclei. J Nutr 122:1085-95
Sidransky, H; Verney, E; Kurl, R (1990) Comparison of effects of L-tryptophan and a tryptophan analog, D,L-beta-(1-naphthyl)alanine, on processes relating to hepatic protein synthesis in rats. J Nutr 120:1157-62
Sidransky, H (1990) Possible role of dietary proteins and amino acids in atherosclerosis. Ann N Y Acad Sci 598:464-81
Sidransky, H; Verney, E; Kurl, R N (1989) Effect of feeding a choline-deficient diet on the hepatic nuclear response to tryptophan in the rat. Exp Mol Pathol 51:68-79
Sidransky, H; Verney, E; Kurl, R N et al. (1988) Effect of tryptophan on toxic cirrhosis induced by intermittent carbon tetrachloride intoxication in the rat. Exp Mol Pathol 49:102-10
Kurl, R N; Holmes, S C; Verney, E et al. (1988) Nuclear envelope glycoprotein with poly(A) polymerase activity of rat liver: isolation, characterization, and immunohistochemical localization. Biochemistry 27:8974-80
Kurl, R N; Verney, E; Sidransky, H (1988) Identification and immunohistochemical localization of a tryptophan binding protein in nuclear envelopes of rat liver. Arch Biochem Biophys 265:286-93