Department of Pathology and Laboratory of Medicine, University of Cincinnati Medical Center, 231 Albert Sabin Way, Cincinnati, OH 45267, USA.
Rejuvenation Res. 2011 Aug;14(4):393-403. doi: 10.1089/rej.2010.1129. Epub 2011 May 19.
Abstract improved growth characteristics of the aging bone marrow cells subsequent to neuropeptide Y (NPY)/neuropeptide Y Y5 receptor (NPY Y5R) ligand-receptor interaction. Bone marrow cells were isolated from neonatal (2-3 weeks), young (8-12 weeks), and old (24-28 months) rats on the basis of their preferential adherence to plastic surface. After culturing the cells at initial seeding density of 1×10(4) cells/cm(2), we found that the proliferation potential of bone marrow cells declined with age. Real-time polymerase chain reaction (PCR) and Western blotting showed that bone marrow cells in different age groups constitutively expressed NPY and NPY receptor subtypes (Y1R, Y2R, and Y5R). However, NPY and Y5R expression increased by more than 130-fold and decreased by 28-fold, respectively, in old bone marrow cells as compared to young bone marrow cells. NPY (10 nM) stimulated the proliferation of all bone marrow cells age groups, and their proliferation was blocked by Y5R antagonist. However, the pro-proliferative effect of NPY on old bone marrow cells was weaker than other cell groups due to lower Y5R expression. Y5R gene transfection of old bone marrow cells with subsequent NPY(3-36) (10 nM) treatment significantly increased proliferation of old bone marrow cells (>56%) as compared to green fluorescence protein-transfected control old bone marrow cells. Stimulation of old bone marrow cells by NPY treatment rejuvenated the growth characteristics of aging bone marrow cells as a result of Y5R overexpression.
神经肽 Y（NPY）/神经肽 Y Y5 受体（NPY Y5R）配体-受体相互作用后，衰老骨髓细胞的生长特性得到改善。根据其对塑料表面的优先黏附性，从新生（2-3 周）、年轻（8-12 周）和老年（24-28 个月）大鼠的骨髓中分离出骨髓细胞。在初始接种密度为 1×10(4)细胞/cm(2)的情况下培养细胞后，我们发现骨髓细胞的增殖潜能随年龄增长而下降。实时聚合酶链反应（PCR）和 Western blot 显示，不同年龄组的骨髓细胞均表达 NPY 和 NPY 受体亚型（Y1R、Y2R 和 Y5R）。然而，与年轻骨髓细胞相比，老年骨髓细胞中的 NPY 和 Y5R 表达分别增加了 130 多倍和减少了 28 倍。NPY（10 nM）刺激所有骨髓细胞年龄组的增殖，其增殖被 Y5R 拮抗剂阻断。然而，由于 Y5R 表达较低，NPY 对老年骨髓细胞的促增殖作用弱于其他细胞群。用 NPY(3-36)（10 nM）处理随后进行 Y5R 基因转染的老年骨髓细胞，与绿色荧光蛋白转染的老年骨髓细胞对照相比，显著增加了老年骨髓细胞的增殖（>56%）。NPY 处理刺激老年骨髓细胞可使衰老骨髓细胞的生长特性年轻化，这是由于 Y5R 过表达。
