Figure 1.
Tumor inoculated transgenic MCK-PGC-1α mice maintain upregulation of PGC-1α and mitochondrial markers.
A. mRNA levels (ΔΔCt) of Ppargc1a in gastrocnemius and quadriceps normalized to Gapdh at 4 months-of-age in MCK-PGC-1α and controls without and with tumor implantation (n = 4/group). B, C. Left panel: Representative Western blotting analysis of steady state levels of PGC-1α and mitochondrial proteins (complex II subunit SDHA, complex III subunit UQCRC1, and complex I subunit NDUFB8) at 4 months-of-age from muscle homogenates of MCK-PGC-1α and controls. Right panel: Optical density (O.D.) quantification of proteins of interest normalized toα tubulin (n = 3/group in B, n = 4/group in C). Error bars are mean ± SEM.
Figure 2.
Tumor injected transgenic MCK-PGC-1α mice maintain upregulation of mtDNA levels and mitochondrial enzymes activity.
A. mtDNA copy number of gastrocnemius and quadriceps of 4-months-old MCK-PGC-1α and wild-type mice, without and with tumor implantation (n = 5/group). B–C. COX and CS enzymatic activity of gastrocnemius (B) and quadriceps (C) muscle homogenates normalized to protein from tumor MCK-PGC-1α and age-matched controls (n = 5/group). D–E. mRNA levels (ΔΔCt) of Ppara, Pparg, Ppard, and Ppargc1b in gastrocnemius (D) and quadriceps (E) normalized to Gapdh at 4-months-old tumor MCK-PGC1–α and aged-matched controls (n = 4/group). Error bars are mean ± SEM.
Figure 3.
Over-expression of MCK-PGC–1α does not protect against cancer-induced cachexia.
A. Percentage body weight over two weeks after tumor cell or saline injection for MCK-PGC-1α or controls at 4 months-of-age, numbers of animals as labeled. B. Percentage tumor-free body weight at 2 weeks after tumor inoculation of MCK-PGC-1α and age-matched controls, numbers of animals as in panel A. C. Weight of tumor (grams) extracted from site of injection 2 weeks after tumor inoculation (n = 5 for wild-type, n = 7 for MCK-PGC-1α). D. Linear regression modeling relationship between changes in percentage body weight and the weight of tumor of MCK-PGC-1α and age-matched tumor-bearing controls, numbers of animals as in panel C. E. Weight of gastrocnemius and quadriceps (grams) of saline-injected and tumor-inoculated groups of MCK-PGC-1α or age-matched wild-type mice, numbers of animals as in panel A. F. Concentrations of serum IL-6 in control and tumor-bearing wild-type and MCK-PGC-1α mice (n = 5/group). Error bars are mean ± SEM.