Abstract The present study investigated autophagy changes and the expression of HMGB1 in human glioblastoma cells, responding to carbon-ion beam irradiation (35 keV/μm, 80.55 MeV/u). U251 cells were irradiated with carbon-ion beams and cell proliferation was measured by counting the number of living cells. The expression of Light Chain 3 beta (LC3B), Beclin 1, high-mobility-group box 1 (HMGB1), pro-form caspase-3 and Cellular FLICE-like inhibitory protein (c-FLIP) was analyzed by western blotting. Caspase enzyme activity was determined via a caspase cleavage based florescent substrate commercial Kit. Living cell counting demonstrated a time- and dose-dependent cell death in U251 cells. The expression of LC3B and Beclin 1 revealed that, a high level of autophagy was induced 24 h after irradiation with 1 Gy carbon ions and then decreased in a time- and dose-dependent manner. The expression of the whole HMGB1 showed a well correlation with the dynamic autophagic level. Cytoplasmic HMGB1 maintained autophagy was concluded. Enzyme-Linked Immuno Sorbent Assay (ELISA) measurement found that, HMGB1 was released into the extracellular space in a time- and dose-dependent manner. Lower intracellular HMGB1 levels correlated with decreased autophagy as measured by the expression of LC3B. Decreased expression of pro-form caspase-3 and c-FLIP as well as the increased caspase enzyme activity indicated that apoptosis was induced by carbon-ion beam irradiation. Inhibition of HMGB1 release from the area of intracellular to that of extracellular significantly increased cell survival. In summary, carbon-ion beam irradiation could elevate autophagy and HMGB1 expression efficiently, which would protect the cells from programmed cell death via inducing autophagy. Apoptosis as measured by expression of caspase activities increased as the dose increased, which was accompanied with decreased levels of LC3B and HMGB1.

    Highlights Carbon-ion irradiation could induce autophagy efficiently. Apoptosis would be promoted accompanied by reduced autophagy. Change of HMGB1 shows a good correlation to the autophagic level. Accumulated HMGB1 protects cell from carbon-ion beam irradiation induced cell death.


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    Title :

    HMGB1 mediated autophagy protects glioblastoma cells from carbon-ion beam irradiation injury


    Contributors:
    Lei, Runhong (author) / Yan, Liben (author) / Deng, Yulin (author) / Xu, Jin (author) / Zhao, Tuo (author) / Awan, M. Umer Farooq (author) / Li, Qiang (author) / Zhou, Guangming (author) / Wang, Xiao (author) / Ma, Hong (author)

    Published in:

    Acta Astronautica ; 166 ; 628-634


    Publication date :

    2019-03-16


    Size :

    7 pages




    Type of media :

    Article (Journal)


    Type of material :

    Electronic Resource


    Language :

    English




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