|Oliver, William - BAYLOR COLL OF MEDICINE|
|Lopez, Rusmely - BAYLOR COLL OF MEDICINE|
|Yorks, Kelsey - BAYLOR COLL OF MEDICINE|
Submitted to: Federation of American Societies for Experimental Biology Conference
Publication Type: Abstract Only
Publication Acceptance Date: March 7, 2006
Publication Date: April 1, 2006
Citation: Oliver, W.T., Lopez, R., Yorks, K.A., Fiorotto, M.L. 2006. Regulation of ERK expression by muscle IGF-I "in vivo" determines the capacity for myonuclear proliferation [abstract]. The Federation of American Societies for Experimental Biology Conference: Advancing the Biomedical Frontier, April 1-5, 2006, San Francisco, California. 20(5):Part II, p. A1046. Technical Abstract: Local IGF-I enhances muscle growth by stimulating protein synthesis and myonuclear accretion. This response, however, is not sustained upon chronic exposure to high levels of IGF-I, and we determined previously that this limited response was associated with a decrease in the amount of muscle ERK protein. We hypothesized that ERK activation was essential for IGF-I stimulation of myonuclear proliferation, and that normal or high levels of expression would be present at the time of accelerated muscle growth. Transgenic mice with high muscle-specific expression of IGF-I (SIS2, n=20) and wildtype (Wt, n=21) controls at 3, 5, and 10 wk of age were injected with either saline or one of 3 doses (0.05, 0.125, or 0.5 mg/kg BW) of LR3-IGF-I (LR3). Mice were killed five minutes later and quadriceps were recovered. ERK 1/2 abundance and degree of tyrosine phosphorylation were measured by Western blot analysis. "In vivo" DNA synthesis was assessed from the incorporation of "methyl"H-thymidine (0.5 mCi/kg bw; 6.7 mCi/mmol) into muscle DNA over one hour. No genotype differences were observed in total ERK protein (P > 0.12) or ERK phosphorylation at 3wk of age. Incorporation of H-thymidine into muscle DNA was 55 and 20% higher in SIS2 than Wt mice at 3 and 5 wks of age (P < 0.001 and P < 0.01), respectively, but not at 10 wk of age (P = 0.95). These data suggest that when ERK is present at normal levels it enables IGF-I to stimulate nuclear proliferation. However, chronic exposure to high IGF-I down-regulates ERK abundance, thereby mitigating the effect of other stimulated pathways on cell division.