Abstract

The long-term goal of the proposed research is a better understanding of the molecular mechanism of the aging process and its relationship to changing endocrine environment.
This aim will be pursued through the regulatory studies on the age- and hormone-dependent synthesis of a hepatic protein (SMP-2). SMP-2 has been identified and characterized as a biomarker for hormone action and aging. The proposed research will emphasize the following: 1) isolation and characterization of full length SMP-2 cDNA clones for two isoforms of SMP-2 using an expression vector; 2) isolation and characterization of the genomic clones for SMP-2; 3) identification of nuclear nonhistone proteins that may show high affinity for the regulatory region of SMP-2 gene; 4) identification of the SMP-2 synthesizing hepatocytes by the immunohistochemical method in order to explore possible cellular specialization in the synthesis of SMP-2; 5) producation of monoclonal antibodies to the both forms of SMP-2; 6) elucidation of the mechanism of androgenic repression of SMP-2 and its mRNA using such experiments as nuclear run off assays, and pulse-chase studies for analysis of mRNA stability; 7) exploration of possible tissue diversity in the synthesis of SMP-2 using RNA dot blot assay and immunohistochemistry; and 8) investigation of the time course of reappearance of SMP-2 at the old age, in caloric restricted rats, by measuring the SMP-2 mRNA level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG003527-08
Application #
3114773
Study Section
Physiological Chemistry Study Section (PC)
Project Start
1988-02-01
Project End
1991-04-30
Budget Start
1989-08-01
Budget End
1991-04-30
Support Year
8
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
University of Texas Health Science Center San Antonio
Department
Type
Overall Medical
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229

  Publications

Song, C S; Jung, M H; Kim, S C et al. (1998) Tissue-specific and androgen-repressible regulation of the rat dehydroepiandrosterone sulfotransferase gene promoter. J Biol Chem 273:21856-66
Chatterjee, B; Song, C S; Jung, M H et al. (1996) Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice. Proc Natl Acad Sci U S A 93:728-33
Chatterjee, B; Song, C S; Kim, J M et al. (1994) Androgen and estrogen sulfotransferases of the rat liver: physiological function, molecular cloning, and in vitro expression. Chem Biol Interact 92:273-9
Song, C S; Her, S; Slomczynska, M et al. (1993) A distal activation domain is critical in the regulation of the rat androgen receptor gene promoter. Biochem J 294 ( Pt 3):779-84
Demyan, W F; Song, C S; Kim, D S et al. (1992) Estrogen sulfotransferase of the rat liver: complementary DNA cloning and age- and sex-specific regulation of messenger RNA. Mol Endocrinol 6:589-97
Mancini, M A; Song, C S; Rao, T R et al. (1992) Spatio-temporal expression of estrogen sulfotransferase within the hepatic lobule of male rats: implication of in situ estrogen inactivation in androgen action. Endocrinology 131:1541-6
Song, C S; Rao, T R; Demyan, W F et al. (1991) Androgen receptor messenger ribonucleic acid (mRNA) in the rat liver: changes in mRNA levels during maturation, aging, and calorie restriction. Endocrinology 128:349-56
Mancini, M A; Chatterjee, B; Roy, A K (1991) Age-dependent reversal of the lobular distribution of androgen-inducible alpha 2u globulin and androgen-repressible SMP-2 in rat liver. J Histochem Cytochem 39:401-5
Song, C S; Kim, J M; Roy, A K et al. (1990) Structure and regulation of the senescence marker protein 2 gene promoter. Biochemistry 29:542-51
Chatterjee, B; Mancini, M A; Roy, A K (1990) The senescence marker protein (SMP-2) of the rat liver: purification, immunochemical characterization and age-dependent regulation. Biochim Biophys Acta 1034:162-9

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