Participation of altered upstream stimulatory factor in the induction of rat heme oxygenase-1 by cadmium.

Abstract:

:We have reported that an upstream stimulatory factor (USF) binding site is functional in transcription of the heme oxygenase-1 gene. In this study, we examined the role of USF in the induced state. By transient expression analyses with the chloramphenicol acetyl-transferase gene, we found that the USF binding site plays an important role in the induction of rat heme oxygenase-1 by cadmium, but not by hemin. To elucidate the role of USF, we prepared USF-rich nuclear extracts from control and cadmium-treated rat liver. On electrophoretic mobility shift assay using control nuclear proteins, one slowly migrating band was detected, whereas using nuclear proteins of cadmium-treated rat liver, two fast migrating bands were detected. The molecular masses of the two subunits of USF prepared from cadmium-treated rat liver were approximately 34 kDa as determined by UV cross-linking and subsequent SDS-PAGE, while the two subunits of native USF were 43 kDa and 44 kDa. DNase I footprinting analysis revealed that both the nuclear proteins bound to the same region including the USF binding site. We therefore suppose that cadmium causes some structural changes in the two proteins of USF and that the altered USF participates in the effective initiation of transcription of the rat heme oxygenase-1 gene.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Maeshima H,Sato M,Ishikawa K,Katagata Y,Yoshida T

doi

10.1093/nar/24.15.2959

subject

Has Abstract

pub_date

1996-08-01 00:00:00

pages

2959-65

issue

15

eissn

0305-1048

issn

1362-4962

pii

6c0070

journal_volume

24

pub_type

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