Abstract

Specific alterations in IGF-I, IGF-II and albumin gene expression are observed in animals that are growth-arrested due to nutritional insufficiency. At least part of the reduction in mRNA is post-transcriptional. Studies of nutritional regulation of albumin synthesis will include an analysis of the effect of amino acid restriction on albumin mRNA stability. Other experiments will involve site-directed mutagenesis of a cloned full-length albumin cDNA, to test the hypothesis that the defect leading to decreased albumin mRNA abundance in amino acid-restricted cells in impaired translation of albumin mRNA. Additionally, regulation of albumin gene expression by protein restriction in intact animals will be studied in Nagase analbuminemic rats and in transgenic mice expressing an albumin minigene or mutant constructs of the albumin minigene. Studies of the nutritional regulation of IGF-II synthesis will include analysis of the effects of amino acid restriction of IGF-II mRNA stability, and identification of sequences in the 3'-untranslated region of IGF-II mRNA which are involved in its regulation by amino acid availability. The normal pathway for IGF- II mRNA degradation will be compared with the pathway utilized in amino acid-restricted cells. The effect of amino acid restriction of IGF-I mRNA abundance and gene transcription will be studied in cultured rat hepatocytes. It will be determined if sequences in the long 3'- untranslated region of the 8 kb species of IGF-I mRNA are involved in its regulation in amino acid-restricted cultured cells.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK039739-06
Application #
2141034
Study Section
Endocrinology Study Section (END)
Project Start
1989-03-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost

  Institution

Name
University of California Riverside
Department
Type
Schools of Medicine
DUNS #
City
Riverside
State
CA
Country
United States
Zip Code
92521

  Publications

Bui, T; Kuo, C; Rotwein, P et al. (1997) Prostaglandin A2 specifically represses insulin-like growth factor-I gene expression in C6 rat glioma cells. Endocrinology 138:985-93
Marten, N W; Sladek, F M; Straus, D S (1996) Effect of dietary protein restriction on liver transcription factors. Biochem J 317 ( Pt 2):361-70
Hayden, J M; Straus, D S (1995) IGF-I and serine protease inhibitor 2.1 nuclear transcript abundance in rat liver during protein restriction. J Endocrinol 145:397-407
Marten, N W; Burke, E J; Hayden, J M et al. (1994) Effect of amino acid limitation on the expression of 19 genes in rat hepatoma cells. FASEB J 8:538-44
Hayden, J M; Marten, N W; Burke, E J et al. (1994) The effect of fasting on insulin-like growth factor-I nuclear transcript abundance in rat liver. Endocrinology 134:760-8
Straus, D S; Marten, N W; Hayden, J M et al. (1994) Protein restriction specifically decreases the abundance of serum albumin and transthyretin nuclear transcripts in rat liver. J Nutr 124:1041-51
Straus, D S (1994) Nutritional regulation of hormones and growth factors that control mammalian growth. FASEB J 8:6-12
Straus, D S; Burke, E J; Marten, N W (1993) Induction of insulin-like growth factor binding protein-1 gene expression in liver of protein-restricted rats and in rat hepatoma cells limited for a single amino acid. Endocrinology 132:1090-100
Tseng, L Y; Ooi, G T; Brown, A L et al. (1992) Transcription of the insulin-like growth factor-binding protein-2 gene is increased in neonatal and fasted adult rat liver. Mol Endocrinol 6:1195-201
Straus, D S; Ooi, G T; Orlowski, C C et al. (1991) Expression of the genes for insulin-like growth factor-I (IGF-I), IGF-II, and IGF-binding proteins-1 and -2 in fetal rat under conditions of intrauterine growth retardation caused by maternal fasting. Endocrinology 128:518-25

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