文献类型： 外文期刊

作者： Hou, Jingang ¹ ; Yun, Yeejin ² ; Xue, Jianjie ³ ; Sun, Mengqi ⁵ ; Kim, Sunchang ¹ ;

作者机构： 1.Korea Adv Inst Sci & Technol, Intelligent Synthet Biol Ctr, Daejeon 34141, South Chungcheo, South Korea

2.Korea Adv Inst Sci & Technol, Dept Biol Sci, 291 Daehak Ro, Daejeon 34141, South Chungcheo, South Korea

3.Qingdao Municipal Ctr Dis Control & Prevent, Qingdao 266033, Shandong, Peoples R China

4.Qingdao Inst Prevent Med, Qingdao 266033, Shandong, Peoples R China

5.Jilin Acad Agr Sci, Changchun 130033, Jilin, Peoples R China

关键词： D-galactose; astrocytic CRT cells; senescence; brain tumor; chemoresistance

期刊名称：MOLECULAR MEDICINE REPORTS （ 影响因子：2.952； 五年影响因子：2.754 ）

ISSN： 1791-2997

年卷期： 2019 年 20 卷 5 期

页码：

收录情况： SCI

摘要： The administration of D-galactose triggers brain aging by poorly understood mechanisms. It is generally recognized that D-galactose induces oxidative stress or affects protein modifications via receptors for advanced glycated end products in a variety of species. In the present study, we aimed to investigate the involvement of astrocytes in D-galactose-induced brain aging in vitro. We found that D-galactose treatment significantly suppressed cell viability and induced cellular senescence. In addition, as of the accumulation of senescent cells, we proposed that the senescence-associated secretory phenotype (SASP) can stimulate age-related pathologies and chemoresistance in brain. Consistently, senescent astrocytic CRT cells induced by D-galactose exhibited increases in the levels of IL-6 and IL-8 via NF-kappa B activation, which are major SASP components and inflammatory cytokines. Conditioned medium prepared from senescent astrocytic CRT cells significantly promoted the viability of brain tumor cells (U373-MG and N2a). Importantly, conditioned medium greatly suppressed the cytotoxicity of U373-MG cells induced by temozolomide, and reduced the protein expression levels of neuron marker neuron-specific class III beta-tubulin, but markedly increased the levels of c-Myc in N2a cells. Thus, our findings demonstrated that D-galactose treatment might mimic brain aging, and that D-galactose could contribute to brain inflammation and tumor progression through inducing the accumulation of senescent-secretory astrocytes.