Figure 6.

Pyruvate & malate supported mitochondrial respiration in tibialis anterior and diaphragm muscle of epithelial ovarian cancer (EOC) injected mice. ADP-stimulated (State III) respiration supported by pyruvate (5 mM) and malate (2 mM) generating NADH was assessed in the absence (-creatine) and presence (+creatine) of creatine within tibialis anterior and diaphragm PmFBs of EOC injected mice. Mitochondrial respiration in the absence of creatine was assessed at submaximal concentrations (25 μM, 100 μM and 500 μM) in tibialis anterior of EOC injected (A). Mitochondrial respiration in the presence of creatine was also assessed at submaximal concentrations (25 μM, 100 μM and 500 μM) in tibialis anterior of EOC injected (B). A schematic representative summary of changes in -Creatine/+Creatine pathways is depicted (C). This was repeated for the diaphragm (D–F) Results represent mean ± SD. n = 9–12. α p < 0.05 Control versus 45 Day; β p < 0.05 Control versus 75 Day; δ p < 0.05 Control versus 90 Day; θ p < 0.05 45 Day versus 90 Day; λ p < 0.05 75 Day vs 90 Day; ∗p < 0.05 Control versus all time points; & p < 0.05 45 Days versus all time points; #p < 0.05 75 Days versus all time points; $ p < 0.05 90 Days versus all time points. All ANOVAs were followed by a two-stage step-up method of Benjamini, Krieger and Yukutieli multiple comparisons test. Voltage dependent anion channel (VDAC); adenine nucleotide translocator (ANT); mitochondrial creatine kinase (mtCK); adenosine diphosphate (ADP); adenosine triphosphate (ATP); phosphocreatine (PCr); creatine (Cr); creatine-independent phosphate shuttling (-Creatine); creatine-dependent phosphate shuttling (+Creatine). All data was analyzed suing a two-way ANOVA (main effects shown only). C57BL/6J female mice ∼75 days post PBS injection as controls (CTRL); C57BL/6J female mice ∼45 days post ovarian cancer injection (45 Days); C57BL/6J female mice ∼75 days post ovarian cancer injection (75 Days); C57BL/6J female mice ∼90 days post ovarian cancer injection (90 Days).