Udagawa Jun, Ono Atsuki, Kawamoto Mai, Otani Hiroki
Department of Developmental Biology, Shimane University, Izumo, Japan.
Neuroreport. 2010 Dec 29;21(18):1140-5. doi: 10.1097/WNR.0b013e328340a74d.
Leptin is associated with the maintenance of epidermal growth factor (EGF)-reactive neural lineage cells, including the neural progenitors. One-day treatment with leptin (10, 100, or 1000 ng/ml) followed by EGF treatment increased the number of small-sized and mid-sized colonies compared with the nonleptin treatment. Leptin prevented the inactivation of the phosphatidylinositol 3-kinase (PI3 K) and extracellular signal regulated kinase (ERK) pathways in neurosphere cells cultured in the non-EGF medium. Bromodeoxyuridine (BrdU) incorporation into the neurosphere cells induced by leptin was suppressed by LY294002, a PI3 K inhibitor, but not by U0126, a MEK1/2 inhibitor, which activates ERK1/2, although U0126 decreased phosphorylated extracellular signal regulated kinase levels. These results suggest that leptin maintains the self-renewal ability and EGF reactivity of immature neural lineage cells and the signal is mediated, at least in part, by the PI3 K pathway.
瘦素与包括神经祖细胞在内的表皮生长因子（EGF）反应性神经谱系细胞的维持有关。与未用瘦素处理相比，用瘦素（10、100或1000 ng/ml）处理一天后再用EGF处理，可增加小型和中型集落的数量。瘦素可防止在无EGF培养基中培养的神经球细胞中磷脂酰肌醇3激酶（PI3K）和细胞外信号调节激酶（ERK）途径的失活。PI3K抑制剂LY294002可抑制瘦素诱导的神经球细胞中溴脱氧尿苷（BrdU）的掺入，但激活ERK1/2的MEK1/2抑制剂U0126则无此作用，尽管U0126可降低磷酸化的细胞外信号调节激酶水平。这些结果表明，瘦素维持未成熟神经谱系细胞的自我更新能力和EGF反应性，且该信号至少部分由PI3K途径介导。
