Abstract
TGF-beta 1 controls the expression of numerous genes, including early response and cellular matrix genes. However, the signal-transducing mechanism underlying this regulation of gene expression is not fully understood. In this study, we investigated whether redox regulation plays a role in the TGF-beta 1 signal transduction in the mouse osteoblastic cell line (MC3T3-E1). The overall intracellular oxidized state of the cells, when measured using 2',7'-dichlorofluorescin diacetate by laser-scanning confocal microscopy, was increased transiently after the addition of TGF-beta 1. This increase was abolished by the addition of oxygen radical scavengers such as catalase and N-acetylcysteine. In a variant cell line lacking the TGF-beta 1 receptor, the intracellular oxidized state was not modulated by treatment with TGF-beta 1. We then examined the expression of early growth response-1 (egr-1) gene, which is inducible by TGF-beta 1 and H2O2. Radical scavengers inhibited the induction of egr-1 by TGF-beta 1, but not that by 12-O-tetradecanoylphorbol-13 acetate. A nuclear run-on assay indicated that this inhibition was at the transcriptional level. From transient expression experiments using chloramphenicol acetyltransferase gene linked to serially deleted egr-1 gene 5'-upstream region, the CArG element in the 5' flanking region of egr-1 was identified as an essential sequence in the transcriptional activation for both TGF-beta 1 and H2O2 stimulation. These findings suggest that H2O2 acts as a mediator for the TGF-beta 1-induced transcription of egr-1 gene.
Dates
Type | When |
---|---|
Created | 21 years, 3 months ago (May 14, 2004, 8:22 p.m.) |
Deposited | 2 years, 1 month ago (July 22, 2023, 1:34 a.m.) |
Indexed | 1 month, 3 weeks ago (July 7, 2025, 1:45 a.m.) |
Issued | 31 years ago (Aug. 15, 1994) |
Published | 31 years ago (Aug. 15, 1994) |
Published Online | 31 years ago (Aug. 15, 1994) |
Published Print | 31 years ago (Aug. 15, 1994) |
@article{Ohba_1994, title={Production of hydrogen peroxide by transforming growth factor-beta 1 and its involvement in induction of egr-1 in mouse osteoblastic cells.}, volume={126}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.126.4.1079}, DOI={10.1083/jcb.126.4.1079}, number={4}, journal={The Journal of cell biology}, publisher={Rockefeller University Press}, author={Ohba, M and Shibanuma, M and Kuroki, T and Nose, K}, year={1994}, month=aug, pages={1079–1088} }