Phorbol myristate acetate induces cellular senescence in rat microglia in vitro

  • Authors:
    • Dan Cao
    • Xiao-Hong Li
    • Xiao-Guang Luo
    • Hong-Mei Yu
    • Li-Shu Wan
    • Ling Wei
    • Yan Ren
  • View Affiliations

  • Published online on: April 23, 2020     https://doi.org/10.3892/ijmm.2020.4587
  • Pages: 415-426
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Abstract

The present study aimed to establish a cellular model to test the hypothesis that oncogene-induced senescence (OIS) is triggered by aging-related activation of microglia. Primary microglia were incubated with phorbol 12-myristate 13-acetate (PMA), and β-galactosidase (β-Gal) staining was applied to subsequent assessment of cellular senescence. Moreover, flow cytometry was employed for examinations of cell cycle arrest and senescence-associated proteins, p53 and p21 were measured by western blotting. Furthermore, examination of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were carried out with microglia supernatants undergoing age-related degenerative diseases in the nervous system, using ELISA. PC12 cells were co-cultured with microglia activated by aging-related alteration(s) to evaluate whether apoptosis was increased in PC12 cells. Cellular senescence-associated β-Gal staining showed that microglial β-Gal expression gradually increased with prolonged PMA stimulation. Microglia in the group receiving 72 h of PMA stimulation displayed the highest percentage of cells arrested in G0/G1, the highest amount of senescence-associated expression of p53 and p21, and the most prominent secretion of TNF-α and IL-1β. In comparison with controls, an increase of apoptotic PC12 cells was detected, which were co-cultured with aging microglia. Taken together, microglia tend to undergo senescence after PMA treatment, suggesting that microglial senescence is associated with inactivation of certain oncogenes.
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July 2020
Volume 46 Issue 1

Print ISSN: 1107-3756
Online ISSN:1791-244X

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APA
Cao, D., Li, X., Luo, X., Yu, H., Wan, L., Wei, L., & Ren, Y. (2020). Phorbol myristate acetate induces cellular senescence in rat microglia in vitro. International Journal of Molecular Medicine, 46, 415-426. https://doi.org/10.3892/ijmm.2020.4587
MLA
Cao, D., Li, X., Luo, X., Yu, H., Wan, L., Wei, L., Ren, Y."Phorbol myristate acetate induces cellular senescence in rat microglia in vitro". International Journal of Molecular Medicine 46.1 (2020): 415-426.
Chicago
Cao, D., Li, X., Luo, X., Yu, H., Wan, L., Wei, L., Ren, Y."Phorbol myristate acetate induces cellular senescence in rat microglia in vitro". International Journal of Molecular Medicine 46, no. 1 (2020): 415-426. https://doi.org/10.3892/ijmm.2020.4587