The Effects of ApoE Knock Out on Skeletal Muscle Regeneration: A Look into Markers of Protein Synthesis and Satellite Cell Function

ApoE helps regulate serum cholesterol levels by adding in transport of cholesterol into the cells, as well as, to the liver. ApoE knockout mice (ApoE KO) present a model that demonstrates the effects of hypercholesterolemia. Damage to muscle stimulates a complex regenerative response. The effects of high cholesterol on this regenerative response are not known. PURPOSE: To determine if skeletal muscle regeneration is altered in apoE KO mice by measuring protein synthesis regulator IGF-1, Akt, mTOR, and p70S6K, cell cycle regulator cyclin D1, and myogenic regulatory factors myoD and myogenin. METHODS: Female C57/BL6 (WT) and apoE KO were assigned to wither an uninjured or injured group. To induce skeletal muscle damage the tibialis anterior (TA) was injected with either bupivacaine or phosphate buffered saline (PBS). TA muscle was extracted 3 days post-injection. Quantitative PCR was conducted to determine gene expression for IGF-1, myoD, myogenin, and Cyclin D1. Western blot analysis was performed to quantitate the markers of protein synthesis Akt, mTOR, and p70S6K. RESULTS: IGF-1 gene expression increased 5-fold (p \u3c 0.05) and 3.5-fold (p \u3c 0.05) during skeletal muscle regeneration in WT and aopE-KO mice, respectively. Cyclin D1 increased 1.75-fold (p \u3c 0.05) in WT mice 3 days post-bupivacaine injection. However, cyclin D1 gene expression increased 12-fold (p \u3c 0.05)3 days post-bupivacaine injection in apoE-KO mice. An attenuation of myoD was observed in apoE KO mice, as there was only an 1.5-fold increase occurred in the apoE KO group compared to a 3.5-fold in the WT controls. An increase in the phosphorylated forms of markers of protein synthesis was observed after bupivacaine injection; a 4.44-fold, 2.5-fold, and a 1.0-foldincrease was observed in Akt, mTOR, and p70 respectively. CONCLUSION: A deficiency in the apoE gene has no effect on markers of protein synthesis expression but does however have an effect on cyclin D1 and myoD expression