Figure 4.

Overexpression of SDHC in IL13^TG mice skeletal muscles leads to improved respiration and fatigue tolerance. Muscles from IL13^TG (emphysema) and IL13^WT (WT) mice were electroporated with a construct holding the SDHC-Flag sequence (right leg) and an SDHC-lacking vector (left leg). Both plasmids hold a GFP sequence as electroporation efficiency reporter. Experiments are performed 2 months after electroporation. (Aa) Microscopic evaluation of muscle section demonstrating preservation of histoarchitecture and positive fluorescence after electroporation. Scale bar, 100 μm. (Ab) Western blotting of muscle samples demonstrating expression of Flag sequence in right leg versus negative expression in left leg. GAPDH was used as a lane loading control. (B) SDHC mRNA normalized to GAPDH mRNA was overexpressed in the right versus left TA muscle after electroporation. (C) SDH activity was significantly elevated in in the right versus left TA muscle after electroporation. (D) OCR was significantly elevated in the right versus left EDL muscle after electroporation. (E) Succinate determination in SDHC-overexpressed leg demonstrates values similar to wild-type mice, suggesting abrogation of substrate accumulation in this setting. (F) fatigue resistance was significantly elevated in the right versus left EDL muscle after electroporation. N = 4. *P < 0.05, **P < 0.01, and ***P < 0.001.