Dataset Information

Characterization of the mechanisms of the increase in PPAR? expression induced by digoxin in the heart using the H9c2 cell line.

ABSTRACT:

Background and purpose

Digoxin has been used as an inotropic agent in heart failure for a long time. Troponin I (TnI) phosphorylation is related to cardiac contractility, and the genes are regulated by peroxisome proliferator-activated receptors (PPARs). Our previous studies indicated that cardiac abnormality related to the depressed expression of PPAR? in the hearts of STZ rats is reversed by digoxin. However, the cellular mechanisms for this effect of digoxin have not been elucidated. The aim of the present study was to investigate possible mechanisms for this effect of digoxin using the H9c2 cell line cultured in high glucose (HG) conditions.

Methods

The effects of digoxin on PPAR? expression, intracellular calcium and TnI phosphorylation were investigated in cultured H9c2 cells, maintained in a HG medium, by using Western blot analysis.

Results

Digoxin increased PPAR? expression in H9c2 cells subjected to HG conditions, and increase the intracellular calcium concentration. This effect of digoxin was blocked by BAPTA-AM at concentrations sufficient to chelate calcium ions. In addition, the calcineurin inhibitor cyclosporine A and KN93, an inhibitor of calcium/calmodulin-dependent protein kinase, inhibited this action. Digoxin also increased TnI phosphorylation and this was inhibited when PPAR? was silenced by the addition of RNAi to the cells. Similar changes were observed on the contraction of H9c2 cells.

Conclusion

The results suggest that digoxin appears, through calcium-triggered signals, to reverse the reduced expression of PPAR? in H9c2 cells caused by HG treatment.

SUBMITTER: Chen ZC

PROVIDER: S-EPMC3087139 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Publications

Characterization of the mechanisms of the increase in PPARδ expression induced by digoxin in the heart using the H9c2 cell line.

Chen Zhih-Cherng ZC Yu Bu-Chin BC Chen Li-Jen LJ Cheng Kai-Chun KC Lin Hung Jung HJ Cheng Juei-Tang JT

British journal of pharmacology 20110501 2

<h4>Background and purpose</h4>Digoxin has been used as an inotropic agent in heart failure for a long time. Troponin I (TnI) phosphorylation is related to cardiac contractility, and the genes are regulated by peroxisome proliferator-activated receptors (PPARs). Our previous studies indicated that cardiac abnormality related to the depressed expression of PPARδ in the hearts of STZ rats is reversed by digoxin. However, the cellular mechanisms for this effect of digoxin have not been elucidated. ...[more]

PMID: 21232041

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