MRGD, a MAS-related G-protein Coupled Receptor, Promotes Tumorigenisis and Is Highly Expressed in Lung Cancer

To elucidate the function of MAS-related GPCR, member D (MRGD) in cancers, we investigated the in vitro and in vivo oncogenic function of MRGD using murine fibroblast cell line NIH3T3 in which MRGD is stably expressed. The expression pattern of MRGD in clinical samples was also analyzed. We found that overexpression of MRGD in NIH3T3 induced focus formation and multi-cellular spheroid formation, and promoted tumors in nude mice. In other words, overexpression of MRGD in NIH3T3 induced the loss of contact inhibition, anchorage-independent growth and in vivo tumorigenesis. Furthermore, it was found that the ligand of MRGD, beta-alanine, enhanced spheroid formation in MRGD-expressing NIH3T3 cells. From investigation of clinical cancer tissues, we found high expression of MRGD in several lung cancers by immunohistochemistry as well as real time PCR. Based on these results, MRGD could be involved in tumorigenesis and could also be a novel anticancer drug target

Conversion of brain cytosol profile from fetal to adult type during the perinatal period: Taurine-NAA exchange

Mammals face drastic environmental changes at birth. Appropriate adjustments of various systems must take place rapidly to accommodate this once in a life time event. The brain undergoes significant adjustments as well, the most obvious of which is in its need to meet the drastic increase in energy consumption at the neuronal cell membrane due to the explosive increase in neural activities after birth. Actual changes were found to be taken place in two systems, namely, acid base balance control and cytosolic energy transport. The adjustments are accomplished by converting cytosol microenvironment from a taurine rich fetal type environment to an N-acetyl-aspartate (NAA) rich adult type environment during the post-natal period. High concentrations of taurine are necessary to provide effective buffering in the fetal brain, because the fetus cannot utilize the adult type of pCO2 dependent acid–base balance control system, namely respiration driven pCO2 changes. To accommodate the significantly higher demand of energy consumption at the membrane due to the increased neuronal activities, taurine has to be replaced by NAA, since the latter facilitates HEP transport from mitochondria to the membrane by passive diffusion