Possible activation by the green tea amino acid theanine of mammalian target of rapamycin signaling in undifferentiated neural progenitor cells in vitro

AbstractWe have shown marked promotion of both proliferation and neuronal differentiation in pluripotent P19 cells exposed to the green tea amino acid theanine, which is a good substrate for SLC38A1 responsible for glutamine transport. In this study, we evaluated the activity of the mammalian target of rapamycin (mTOR) kinase pathway, which participates in protein translation, cell growth and autophagy in a manner relevant to intracellular glutamine levels, in murine neural progenitor cells exposed to theanine. Exposure to theanine promoted the phosphorylation of mTOR and downstream proteins in neurospheres from embryonic mouse neocortex. Although stable overexpression of SLC38A1 similarly facilitated phosphorylation of mTOR-relevant proteins in undifferentiated P19 cells, theanine failed to additionally accelerate the increased phosphorylation in these stable transfectants. Theanine accelerated the formation of neurospheres from murine embryonic neocortex and adult hippocampus, along with facilitation of both 5-bromo-2’-deoxyuridine incorporation and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide reduction in embryonic neurospheres. In embryonic neurospheres previously exposed to theanine, a significant increase was seen in the number of cells immunoreactive for a neuronal marker protein after spontaneous differentiation. These results suggest that theanine activates the mTOR signaling pathway for proliferation together with accelerated neurogenesis in murine undifferentiated neural progenitor cells

Age-related dysfunction of the DNA damage response in intestinal stem cells

Abstract Background Senescence increases the risks of inflammatory bowel diseases and colon cancer. Intestinal stem cells (ISCs) in crypts differentiate into epithelial cells and thereby maintain intestinal homeostasis. However, the influence of aging on the functions of ISCs is largely unknown. The mutation rate is highest in the small and large intestines. Numerous types of naturally occurring DNA damage are removed by the DNA damage response (DDR). This response induces DNA repair and apoptosis; therefore, its dysregulation leads to accumulation of damaged DNA and consequently cellular dysfunctions, including tumorigenesis. This study investigated whether aging affects the DDR in mouse ISCs. Methods Young (2–3-month-old) and old (> 19-month-old) Lgr5-EGFP-IRES-creERT2 mice were irradiated. The DDR in Lgr5-positive ISCs was compared between these mice by immunohistochemical analyses. Results Induction of DDR marker proteins (phosphorylated ATR and 53BP1), inflammatory factors (phosphorylated NF-κB and interleukin-6), and a mitochondrial biogenesis-associated gene (peroxisome proliferator-activated receptor-γ coactivator 1α) was lower in old ISCs than in young ISCs in vivo. Conclusion The competence of the DDR in ISCs declines with age in vivo

First pionic atom spectroscopy at RIBF

We have performed an inclusive spectroscopy of 122Sn(d, 3He) reaction near the pion emission threshold at an incident energy of Td = 250 MeV/nucleon. The first experiment aims as devloping the high precision spectroscopy of pionic atoms at the RI beam factory (RIBF) of RIKEN, which leads to a new project, pionic Atom Factory project (piAF) to measure pionic atoms for a wide range of elements. We report the analysis status of the pilot experiment

First pionic atom spectroscopy at RIBF

We have performed an inclusive spectroscopy of 122Sn(d, 3He) reaction near the pion emission threshold at an incident energy of Td = 250 MeV/nucleon. The first experiment aims as devloping the high precision spectroscopy of pionic atoms at the RI beam factory (RIBF) of RIKEN, which leads to a new project, pionic Atom Factory project (piAF) to measure pionic atoms for a wide range of elements. We report the analysis status of the pilot experiment