Substance P Stimulates the Recovery of Bone Marrow After the Irradiation

被引:41
作者
An, You Sun [2 ]
Lee, Eunah [1 ]
Kang, Mi-Hyun [2 ]
Hong, Hyun Sook [1 ]
Kim, Mi-Ra [2 ]
Jang, Won Seok [3 ]
Son, Youngsook [1 ]
Yi, Jae Youn [2 ]
机构
[1] Kyung Hee Univ, Coll Life Sci, Dept Genet Engn, Yongin 446701, Gyeonggi Do, South Korea
[2] Korea Inst Radiat & Med Sci, Lab Modulat Radiobiol Responses, Seoul 139706, South Korea
[3] Korea Inst Radiat & Med Sci, Korea Canc Ctr Hosp, Dept Pathol, Seoul 139706, South Korea
关键词
MESENCHYMAL STEM-CELLS; TOTAL-BODY IRRADIATION; GAMMA-RADIATION; INDUCED DAMAGE; ANAPHYLACTOID REACTION; IONIZING-RADIATION; HUMAN COLONOCYTES; BCL-2; PROTEINS; CANCER CELLS; ANAL CANCER;
D O I
10.1002/jcp.22447
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The therapeutic use of ionizing radiation (e. g., X-rays and gamma-rays) needs to inflict minimal damage on non-target tissue. Recent studies have shown that substance P (SP) mediates multiple activities in various cell types, including cell proliferation, anti-apoptotic responses, and inflammatory processes. The present study investigated the effects of SP on gamma-irradiated bone marrow stem cells (BMSCs). In mouse bone marrow extracts, SP prolonged activation of Erk1/2 and enhanced Bcl-2 expression, but attenuated the activation of apoptotic molecules (e. g., p38 and cleaved caspase-3) and down-regulated Bax. We also observed that SP-decreased apoptotic cell death and stimulated cell proliferation in gamma-irradiated mouse bone marrow tissues through TUNEL assay and PCNA analysis. To determine how SP affects bone marrow stem cell populations, mouse bone marrow cells were isolated and colony-forming unit (CFU) of mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) was estimated. SP-pretreated ones showed higher CFUs of MSC and HSC than untreated ones. Furthermore, when SP was pretreated in cultured human MSC, it significantly decreased apoptotic cells at 48 and 72 h after gamma-irradiation. Compared with untreated cells, SP-treated human MSCs showed reduced cleavage of apoptotic molecules such as caspase-8, -9, -3, and poly ADP-ribose polymerase (PARP). Thus, our results suggest that SP alleviates gamma-radiation-induced damage to mouse BMSCs and human MSCs via regulation of the apoptotic pathway. J. Cell. Physiol. 226: 1204-1213, 2011. (C) 2010 Wiley-Liss, Inc.
引用
收藏
页码:1204 / 1213
页数:10
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