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Our previous studies indicated that cardiac abnormality related to the depressed expression of PPAR\u03b4 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>METHODS<\/jats:title><jats:p>The effects of digoxin on PPAR\u03b4 expression, intracellular calcium and TnI phosphorylation were investigated in cultured H9c2 cells, maintained in a HG medium, by using Western blot analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>RESULTS<\/jats:title><jats:p>Digoxin increased PPAR\u03b4 expression in H9c2 cells subjected to HG conditions, and increase the intracellular calcium concentration. This effect of digoxin was blocked by BAPTA\u2010AM at concentrations sufficient to chelate calcium ions. In addition, the calcineurin inhibitor cyclosporine A and KN93, an inhibitor of calcium\/calmodulin\u2010dependent protein kinase, inhibited this action. Digoxin also increased TnI phosphorylation and this was inhibited when PPAR\u03b4 was silenced by the addition of RNAi to the cells. Similar changes were observed on the contraction of H9c2 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>CONCLUSION<\/jats:title><jats:p>The results suggest that digoxin appears, through calcium\u2010triggered signals, to reverse the reduced expression of PPAR\u03b4 in H9c2 cells caused by HG treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/j.1476-5381.2011.01212.x","type":"journal-article","created":{"date-parts":[[2011,1,14]],"date-time":"2011-01-14T12:26:06Z","timestamp":1295007966000},"page":"390-398","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Characterization of the mechanisms of the increase in PPAR\u03b4 expression induced by digoxin in the heart using the H9c2 cell 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