Endogenous Metabolite X By Activated Erk Pathway Increases Cyclind1 To Promote C <sub> 2 </ Sub> C <sub> 12 </ Sub> Cell Proliferation

In the 1920s, Otto Warburg demonstrated that tumor cells had high rates of glycolysis, lactate production, and biosynthesis of lipids and other macromolecules which have been regarded as the Warburg's effect. Recently, Warburg's effect is being greatly recongnized and identification of novel functional roles of endogenous metabolites is the hot spot in biomedical research.Recently, enzyme Z was identified in a screen for genes whose expression was differentially regulated in the skeletal muscle tissue between broiler and layer chickens by transcriptom and proteomics analysis. In addtiton, our previously unpublished data also demonstrated that the enzymatic activity of the enzyme Z and concerntration of its substrate X were higher in the skeletal muscle tissue of the rapidly growthing broiler than in that of layer chicken. Considering the skeletal muscle is the major organ for utilizing the intrinsic metabolite X, these observations suggest that the intrinsic metabolite X play regulatory roles during skeletal muscle development. Therefore, in the present study, we investigated the effect of the X on muscle cell proliferation and the possible moleculear mechanisms for its function.Herein we provided experimental evidence to show that the intrinsic metabolite X promoted the C2C12 cell proliferation in vitro by upregulating expression of the cyclinD1 via ERK signaling pathway. More interestingly, we found that the X agonized IGF function and antagonized myostatin inhibitory effect on muscle cell proliferation. To ask whether the molecular action of X was dependent on its enzyme Z, the HepG2 cells (an enzyme Z deficiency cell line) was treated by the X and the results indicated that X can still promote HepG2 cell proliferation. In addation, we also investigated the effect of X's product and found that X's product had no effect on C2C12 cell proliferation. Taken together, our findings indicated that the intrinsic metabolite X plays regulatory roles in cell proliferation in the way of independent on its metabolism. Our work highlights the potential application of using the X to cure human diseases, such as muscular dystrophy and atrophy.