Thioredoxin-interacting protein (TXNIP) is a negative regulator of thioredoxin (Trx) activity and is involved in induction of apoptosis and oxidative stress.  Increases in TXNIP have been associated with development of cardiovascular diseases, diabetes, and cancer.  Preliminary Western blot data showed that carvedilol, a nonselective β-blocker used in the treatment of heart failure and hypertension, decreased cytosolic TXNIP in H9c2 rat cardiomyocytes by 40%.  To investigate the mechanism of this reduction, H9c2 cells were treated with carvedilol 10 mM for 24 and 48 hours followed by rt-PCR to measure TXNIP gene expression.  No change in TXNIP mRNA was observed at either time point. Proteasomal degradation of TXNIP was investigated using MG132, a non-specific proteasomal inhibitor. The reduction of TXNIP in the cytosol was still observed in the presence of MG132.  TXNIP is known to be found in the cytosol, nucleus, and mitochondria.  Therefore, Western blot was utilized to determine TXNIP level in these organelles.  In the nuclear fraction, TXNIP was increased by 40% compared to control (p&lt;0.05).  No change was observed in the mitochondrial fraction.  Poly-ADP-ribose polymerase (PARP) is known to be a binding protein for TXNIP in the nucleus. Formation of the TXNIP-PARP complex was investigated using immunoprecipitation.  An increase in the TXNIP- PARP complex in carvedilol treated cells was observed compared to control at 24 hours. These results indicate that carvedilol increases TXNIP localization in the nucleus.  Further studies are needed to determine the mechanism and effects of TXNIP nuclear localization from carvedilol treatment.<br/>

Carvedilol increases nuclear localization of thioredoxin-interacting protein (TXNIP) in H9c2 cells

256th National Meeting (2018)

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