Publications [#180933] of G. Allan Johnson

Papers Published
  1. JY Kim, RC Burghardt, G Wu, GA Johnson, TE Spencer, FW Bazer, Select Nutrients in the Ovine Uterine Lumen. VIII. Arginine Stimulates Proliferation of Ovine Trophectoderm Cells Through MTOR-RPS6K-RPS6 Signaling Cascade and Synthesis of Nitric Oxide and Polyamines., Biology of reproduction (September, 2010) [doi] .

    During the peri-implantation period in sheep, L-arginine (L-Arg) in the uterine lumen is an essential substrate for synthesis of nitric oxide (NO) by nitric oxide synthase (NOS) and polyamines via arginase and ornithine decarboxylase (ODC1) required for survival and development of ovine conceptuses (embryo and its extra-embryonic membranes). L-Arg can stimulate hypertrophy, hyperplasia and differentiation of the ovine conceptus trophectoderm; however, the responsible signal transduction cascade has not been determined. Therefore, this study examined possible signaling pathways mediated by L-Arg, as well as effects of two NO donors, SNAP and DETA, and putrescine (precursor for spermidine and spermine) on oTr cell proliferation. Further, the inhibition of these effects by L-NAME (an inhibitor of NOS) and Nor-NOHA (an inhibitor of arginase) was assessed. L-Arg treatment increased the abundance of phosphorylated MTOR, RPS6K and EIF4EBP1 in oTr cells. Consistent with activation of these cell signaling molecules, L-Arg increased protein synthesis and reduced protein degradation in oTr cells. Both NO and polyamines enhanced cell proliferation in a dose-dependent manner. The effects of L-Arg were partially inhibited by both L-NAME and Nor-NOHA. These results indicate that L-Arg enhances production of polyamines and NO and activates the MTOR/FRAP1-RPS6K-RPS6 signaling pathway to stimulate proliferation and migration of oTr cells.