RGD Reference Report - Vitamin D(3)-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin. - Rat Genome Database

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Vitamin D(3)-up-regulated protein-1 is a stress-responsive gene that regulates cardiomyocyte viability through interaction with thioredoxin.

Authors: Wang, Y  De Keulenaer, GW  Lee, RT 
Citation: Wang Y, etal., J Biol Chem 2002 Jul 19;277(29):26496-500.
RGD ID: 727213
Pubmed: (View Article at PubMed) PMID:12011048
DOI: Full-text: DOI:10.1074/jbc.M202133200

The protein-disulfide reductase thioredoxin is critical for redox signaling during apoptosis and growth. In this study, we demonstrate that vitamin D(3)-up-regulated protein-1 regulates thioredoxin in conditions of biomechanical or oxidative stress and critically regulates cardiomyocyte viability. Expression of vitamin D(3)-up-regulated protein-1 but not of thioredoxin in rat cardiomyocytes was rapidly suppressed by biomechanical strain or hydrogen peroxide at both mRNA and protein levels. Mechanical suppression of vitamin D(3)-up-regulated protein-1 gene expression was blocked by N-acetylcysteine. The half-life of vitamin D(3)-up-regulated protein-1 transcripts in cardiomyocytes was only 1.1 h and remained unchanged after mechanical stimulation, suggesting that rapid responses in vitamin D(3)-up-regulated protein-1 gene expression occur through transcriptional control. Vitamin D(3)-up-regulated protein-1 down-regulation by strain or hydrogen peroxide led to increased thioredoxin activity, whereas adenovirus-mediated overexpression of vitamin D(3)-up-regulated protein-1 suppressed thioredoxin activity. Overexpression of vitamin D(3)-up-regulated protein-1 but not of thioredoxin induced cardiomyocyte apoptosis. Furthermore, overexpression of vitamin D(3)-up-regulated protein-1 sensitized cells to hydrogen peroxide-induced apoptosis, whereas overexpression of thioredoxin protected against injury. These data identify vitamin D(3)-up-regulated protein-1 as a key stress-responsive inhibitory switch of thioredoxin activity in cardiomyocytes and demonstrate that the vitamin D(3)-up-regulated protein-1/thioredoxin axis has an important role in the preservation of cellular viability.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Txn1  (thioredoxin 1)
Txnip  (thioredoxin interacting protein)


Additional Information