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 postranscriptional 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. Also, we plan to investigate how tryptophan acts in improving hepatic protein synthesis in rats treated with hepatotoxic agents. Such information may offer basic insight as to how an important dietary component, as exemplified by L-tryptophan, may plan a regulatory role in mammalian liver protein metabolism.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM027339-06
Application #
3151737
Study Section
Pathology B Study Section (PTHB)
Project Start
1980-09-01
Project End
1986-08-31
Budget Start
1985-09-01
Budget End
1986-08-31
Support Year
6
Fiscal Year
1985
Total Cost
Indirect Cost
Name
George Washington University
Department
Type
Schools of Medicine
DUNS #
City
Washington
State
DC
Country
United States
Zip Code
20052
Sidransky, H; Verney, E (1988) Effect of tryptophan on livers of pregnant and lactating rats and their fetuses and pups. Proc Soc Exp Biol Med 187:309-14
Sidransky, H (1987) Ethanol and liver injury: aspects relating to hepatic protein synthesis. Rev Environ Health 7:81-120
Wang, D; Verney, E; Kurl, R N et al. (1987) Effect of tryptophan on isolated hepatocytes of rats. Virchows Arch B Cell Pathol Incl Mol Pathol 53:125-32
Sidransky, H (1986) Role of tryptophan in carcinogenesis. Adv Exp Med Biol 206:187-207
Sidransky, H; Murty, C N; Verney, E (1986) Evidence for the role of glycosylation of proteins in the tryptophan-induced stimulation of nucleocytoplasmic translocation of mRNA in rat liver. Lab Invest 54:93-9
Sidransky, H; Verney, E; Murty, C N (1986) The influence of hypertonic NaCl on nucleocytoplasmic translocation of RNA in the rat liver. Am J Pathol 123:577-84
Sidransky, H; Robinson, E; Verney, E (1985) Hepatic ornithine decarboxylase activity in the rat as influenced by retinyl acetate and ethanol or tryptophan. Exp Mol Pathol 43:115-23
Wang, D; Verney, E; Sidransky, H (1985) Protective effect of tryptophan and cysteine against carbon tetrachloride-induced liver injury. Exp Mol Pathol 43:364-74
Sidransky, H; Verney, E (1985) Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance. J Exp Pathol 2:47-57