D‑galactose induces astrocytic aging and contributes to astrocytoma progression and chemoresistance via cellular senescence

Hou,Jingang; Yun,Yeejin; Xue,Jianjie; Sun,Mengqi; Kim,Sunchang

doi:10.3892/mmr.2019.10677

D‑galactose induces astrocytic aging and contributes to astrocytoma progression and chemoresistance via cellular senescence

Authors:
- Jingang Hou
- Yeejin Yun
- Jianjie Xue
- Mengqi Sun
- Sunchang Kim
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Affiliations: Intelligent Synthetic Biology Center, Daejeon, South Chungcheong 34141, Republic of Korea, Department of Biological Sciences, KAIST, Daejeon, South Chungcheong 34141, Republic of Korea, Qingdao Municipal Center for Disease Control and Prevention, Qingdao, Shandong 266033, P.R. China, Jilin Academy of Agricultural Sciences, Changchun, Jilin 130033, P.R. China
Published online on: September 12, 2019 https://doi.org/10.3892/mmr.2019.10677
Pages: 4111-4118
Copyright: © Hou et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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‑κB 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 β‑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.

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