FIG 6.
Mitochondrial function is impaired following 10, 21, or 42 days of Akt induction. (A to C) Changes in maximal ADP-stimulated mitochondrial respiration (VADP) (A), ATP synthesis rates (B), and ATP/O ratios (C) in saponin-permeabilized cardiac fibers treated with palmitoyl-carnitine (PC) as the substrate from control (Con) or IND-Akt mice withdrawn from DOX for 10 days (n = 8 or 7), 21 days (n = 6 or 8), 21 days with rapamycin (Rap) (n = 8 or 9), or 42 days (n = 8 or 9), respectively. (D and E) Hydroxyacyl-CoA dehydrogenase (HADH) enzymatic activity (D) and citrate synthase (CS) enzymatic activity (E) from hearts of Con or IND-Akt mice withdrawn from DOX for 10 days (n = 6), 21 days (n = 4), or 21 days plus Rap (n = 3), respectively. (F) Heart weight-to-body weight ratio (HW/BW) of Con or IND-Akt mice withdrawn from DOX for 10 days (n = 7 or 10), 21 days (n = 6 or 9), or 21 days with Rap (n = 8 or 9), respectively. (G to I) Rapamycin alters signaling in IND-Akt hearts withdrawn from DOX. Ratio of phosphorylated p70 S6 kinase at Thr389 (p-T389) to total S6K (H) and ratio of phosphorylated glycogen synthase kinase 3β at Ser9 (p-S9) to total GSK-3β (I) in hearts from control and IND-Akt mice treated daily with rapamycin or vehicle. dfw, dry fiber weight; whw, wet heart weight; n.s., nonspecific band loading control. Data shown as mean ± SEM. *, P < 0.05 versus induction and treatment-matched control; #, P < 0.05 versus vehicle-treated animals of the same genotype.