Developmentally regulated expression of two transcripts for heme oxygenase-2 with a first exon unique to rat testis: control by corticosterone of the oxygenase protein expression

被引:45
作者
Liu, NN
Wang, XJ
McCoubrey, WK
Maines, MD
机构
[1] Univ Rochester, Sch Med, Dept Biochem, Rochester, NY 14642 USA
[2] Univ Rochester, Sch Med, Dept Biophys, Rochester, NY 14642 USA
关键词
development of testis; glucocorticoid control of gene expression; heme oxygenase isozymes; tissue-specific gene expression;
D O I
10.1016/S0378-1119(99)00439-4
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Heme oxygenase (HO)-2, the constitutive cognate of oxidative stress inducible HO-1 (HSP32), degrades heme to biliverdin, carbon monoxide, and iron. The highest levels of HO-2 are found in the testis. Previously we identified multiple HO-2 homologous transcripts that differ in size and use three different 5' UTRs that form the untranslated first exon of the gene (referred to as rHO-2, rHO-2-1 and rHO-2-2) and two poly(A) signals. Also, we have characterized a functional glucocorticoid response element (GRE) in the promoter region of I HO-2. In this study, we have examined the structural basis for size heterogeneity of HO-2 transcripts and whether expression of HO-2 at mRNA and protein levels is subject to regulation by corticosterone. Age and tissue-dependence of transcript expression were examined as well. Our data indicate that the remarkable increase in HO-2 mRNA in adult rat testis is due primarily to generation of two HO-2 homologous transcripts of approx. 2.1 kb and approx. 1.45 kb size that use rHO-2 and are unique to this tissue, and that rHO-2 is not used within other organs. These transcripts are not present in the brain, kidney, thymus, heart, spleen, liver, or in prepubertal 14 day old rat testis. The testis-specific transcripts contain all of the coding region exons present in the approx. 1.3 kb and approx. 1.9 kb transcripts that are common to all organs, including the adult and prepubertal rat testis. Differential use of the poly(A) signals accounts for the difference in size of these two transcripts. Treatment of newborn rats with corticosterone for 5 days, starting on day 2 after birth, induced HO-2 protein expression in the testis as detected by Western blotting. In adult rat testis, corticosterone treatment, however, was not an effective regulator of HO-2 transcript populations or levels. The findings suggest that HO-2 levels in the testis are controlled by glucocorticoids; and that developmental and tissue-specific factor(s) determine generation of transcripts unique to the organ. The apparent exclusive use of rHO-2 by the mature testis is consistent with the possibility that HO-2 may play a role in male reproduction. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:175 / 183
页数:9
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