Figure 3: Characterizing Changes in Mitochondrial Function and Cell Energetics With Sunitinib Treatment

(A) Flow cytometry histogram showing levels of tetramethylrhodamine (TMRM). Neonatal rat ventricular myocytes grown in flat culture were treated with 0.1% dimethyl sulfoxide (vehicle), 1 μmol/l sunitinib, or 50 μmol/l carbonyl cyanide m-chlorophenyl hydrazine (CCCP) for 30 min (CCCP) or 4 h (dimethyl sulfoxide and sunitinib) and then were labeled with 10 nmol/l TMRM. (B) Time-dependent decreases in mitochondria membrane potential following treatment with 1 μmol/l sunitinib. Neonatal rat ventricular myocytes grown in flat culture were treated with 0.1% dimethyl sulfoxide or 1 μmol/l sunitinib for 30 min to 24 h and labeled with TMRM to assess mitochondria membrane potential. *p < 0.05 (n = 3 experiments). (C) Decreases in adenosine triphosphate (ATP) levels in neonatal rat ventricular myocytes following 24 h treatment with 1 μmol/l sunitinib. *p < 0.05 (n = 3 experiments). (D) Upstream activation of adenosine monophosphate-activated protein kinase with molecule 5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside (AICAR) did not reverse sunitinib-induced caspase activation in rat cardiac microtissues (n = 2 experiments). NS = not significant.