2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin induces premature senescence of astrocytes via WNT/β-catenin signaling and ROS production.
2, 3, 7, 8-tetrachlorodibenzo-p-dioxin (TCDD) is a ubiquitous environmental contaminant that could exert significant neurotoxicity in the human nervous system. Nevertheless, the molecular mechanism underlying TCDD-mediated neurotoxicity has not been clarified clearly. Herein, we investigated the potential role of TCDD in facilitating premature senescence in astrocytes and the underlying molecular mechanisms. Using the senescence-associated β-galactosidase (SA-β-Gal) assay, we demonstrated that TCDD exposure triggered significant premature senescence of astrocyte cells, which was accompanied by a marked activation of the Wingless and int (WNT)/β-catenin signaling pathway. In addition, TCDD altered the expression of senescence marker proteins, such as p16, p21 and GFAP, which together have been reported to be upregulated in aging astrocytes, in both dose- and time-dependent manners. Further, TCDD led to cell-cycle arrest, F-actin reorganization and the accumulation of cellular reactive oxygen species (ROS). Moreover, the ROS scavenger N-acetylcysteine (NAC) markedly attenuated TCDD-induced ROS production, cellular oxidative damage and astrocyte senescence. Notably, the application of XAV939, an inhibitor of WNT/β-catenin signaling pathway, ameliorated the effect of TCDD on cellular β-catenin level, ROS production, cellular oxidative damage and premature senescence in astrocytes. In summary, our findings indicated that TCDD might induce astrocyte senescence via WNT/β-catenin and ROS-dependent mechanisms.
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Xiaoke
X
Nie
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Lingwei
L
Liang
Department of Disease Prevention, Second People's Hospital of Nantong, Nantong, Jiangsu Province, 226001, China.
Hanqing
H
Xi
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Shengyang
S
Jiang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Junkang
J
Jiang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Cuiying
C
Tang
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Xipeng
X
Liu
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Suyi
S
Liu
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Chunhua
C
Wan
Department of Nutrition and Food Hygiene, School of Public Health, Nantong University, Nantong, Jiangsu, 226001, China.
Jianya
J
Zhao
Department of Disease Prevention, Second People's Hospital of Nantong, Nantong, Jiangsu Province, 226001, China.
Jianbin
J
Yang
D000818:Animals; D001253:Astrocytes / Q000187:drug effects*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D016922:Cellular Senescence / Q000187:drug effects*; D004249:DNA Damage / Q000187:drug effects; D004147:Dioxins / Q000494:pharmacology* / Q000633:toxicity; D005455:Fluorescent Antibody Technique; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060449:Wnt Signaling Pathway / Q000187:drug effects*
D004147:Dioxins; D017382:Reactive Oxygen Species; C066841:2,3,7,8-tetrabromodibenzo-4-dioxin
2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin; ROS; WNT/β-catenin signaling; aging; astrocyte