Adenosine modulates L-DOPA level during physical activity though NR4A2 (Nurr-1) – TYROSINE HYDROXYLASE–L-DOPA pathway

Abstract

Previously our research team found nine genes (ATF3, NR4A2, NFIL3, NR4A3, MAFF, SIK, SLC2A3, MYC, and SOCS3) that are differentially expressed in sedentary and physically active people. Another study of our team showed an affinity level of gut derived metabolites that interacted with these nine proteins. One of the strongest binding activities was observed between adenosine and NR4A2. NR4A2 is a nuclear orphan factor responsible for adaptation to physical activity and neuronal signaling. As a step towards understanding the mechanism of gut derived metabolites affecting mental function such as motivation to physical activity through gene modulation, this study was performed. To investigate the regulation of L-DOPA level through the NR4A2-TH-L-DOPA pathway through Adenosine, the qPCR analysis and Western blot analysis were used. Rhabdomyosarcoma (RD CCL-136) cells were used as a platform for gene expression analysis. The results showed the ability of adenosine to initiate expression of NR4A2. Further investigation of the proposed mechanism should be performed to clarify expression of NR4A2 in a time and dose dependent manner. The study will elucidate a broader understanding of gut-derived adenosine’s effect on NR4A2-TH-L-DOPA pathway and the potential mechanism of motivation it regulates.