PKC alpha overexpression in cardiomyocytes caused marked repression of triiodothyronine (T3)-responsive genes, alpha-myosin heavy chain, and the sarcoplasmic reticulum calcium-activated adenosinetriphosphatase SERCA2. Treatment with T3 for 4 h resulted in significant reductions of PKC alpha in nuclear and cytosolic compartments, and decreased TR alpha1 mRNA and protein, with normalization of phenotype.