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KMID : 0385219960060010066
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Korean Journal of Gerontology
1996 Volume.6 No. 1 p.66 ~ p.75
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Studies on Dehydroepiandrosterone Sulfotransferase(DST) Gene from Rat Liver
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Kim Dong-Seob
Oh Doo-Hwan
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Abstract
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Liver, which serves essential functions such as production of various proteins and detoxifiacation of xenobiotic materials, is an androgen-sensitive organ. The expression dehydroepiandrosterone Sulfotransferase(DST) from rat liver is not only tissue-, age- and sex-specific, but repressed by androgen. On the other hand, against androgen, DST deprives the function of androgen in the living body by sulfation, and shows side effects such as induction of carcinogenicity of both endogenous and exogenous compounds as well as increase of carcinogenicity of carcinogenic compounds. DST shows distinct 3 stage change that the expression amount of DST decreased and re-increased according to the age in the male rat liver. Therefore DST has been served as a good model system to study aging phenomena. Researches to figure out the properties of DST are still going on in view of protein level, but the results about DST gene have not been published after the report about complementary DNA(cDNA) sequence of DST. In this study, DST gene was isolated from Fischer rat F344 liver and characterized. One of the ten positive clones isolated from gDNA library, using published cDNA as a probe, was named as L12 and used for the material of this dissertation. The DST gene in L12 was composed of 5 exons, showing more than 90% sequence homology to the cDNA, and has an open reading frame (ORF) coding 285 amino acids. Compared with published SMP-2a which has exonⅠ and exonⅡ, the intron after exonⅡ of SMP-2a was absent in L12. Analysis of aligned cDNA sequence of other DSTs shows a putative 3’-phosphoadenosine 5’-phosphoadenosine(PAPS) binding domain during sulfation reaction. In order to find the factors which regulate the change of DST gene expression during aging, sequence homology of promoter region of DST positive clones and DNA-protein binding reaction were studied. The nucleotide sequence of promoter region from different strains did not show strain-specificity, and the DST seemed to be produced by a group of gene family. To see the trans-acting factors and cis-acting elements which regulate gene expression, nuclear extracts prepared from rat liver of different ages were reacted with DST promoter. After band shift and DNaseI footprinting assay, a protein was suspected to be always bound to the DST promoter region, then the change of binding with another protein affects the DST gene expression. In this case, the protein which always binds to the promoter region seemed to be affected by androgen, and this mechanism supposed to be the one of the whole mechanism that basically DST expression was repressed by androgen.
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KEYWORD
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androgen, Dehydroepiandrosterone Sulfotransferase, aging, sulfation, 3’-phosphoadenosine 5’-phosphosulfate
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