RNA reading protein YTHDF2 mediates Benzo(k)fluoranthene induced male reproductive injury by regulating the stability of BCL2.

Autor: Li YW; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China., Wang DD; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Chen HQ; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Zeng Y; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Wang N; School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Shi Y; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; College of Pharmacy & Bioengineering, Chongqing University of Technology, Chongqing, 400054, China., Li JY; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; College of Pharmacy & Bioengineering, Chongqing University of Technology, Chongqing, 400054, China., Zhou NY; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Wang DP; School of Public Health, The Key Laboratory of Environmental Pollution Monitoring and Disease Control, Ministry of Education, Guizhou Medical University, Guiyang, 561113, China., Chen Q; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Han X; Department of Traditional Chinese Medicine Health and Preventive Medicine, Guangzhou University of Traditional Chinese Medicine, Guangzhou, 510006, China., Cao J; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China., Liu WB; Institute of Toxicology, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China; Department of Environmental Health, College of Preventive Medicine, Third Military Medical University (Army Medical University), Chongqing, 400038, China. Electronic address: liuwenbin@tmmu.edu.cn.
Jazyk: angličtina
Zdroj: Environmental pollution (Barking, Essex : 1987) [Environ Pollut] 2024 Nov 15; Vol. 361, pp. 124889. Date of Electronic Publication: 2024 Sep 03.
DOI: 10.1016/j.envpol.2024.124889
Abstrakt: Benzo (k) fluoranthene (BkF) has adverse effects on male reproduction, but its specific mechanism of action is still unclear. This study focused on the role of RNA reading protein YTHDF2 and its mechanism in BkF induced male reproductive injury. Mouse GC-2 spermatocytes were exposed to 0, 40, 80, 160 μM BkF. It was found that BkF significantly increased the apoptosis of GC-2 cell and decreased its survival rate. BCL2 in spermatocytes decreased significantly, while the expression of P53 and BAX exhibited a notable increase. Interestingly, the expression of RNA reading protein YTHDF2 progressively rose in tandem with the escalating BkF exposure dosage. Overexpression of YTHDF2 significantly reduced the viability of cells and increased the apoptosis rate. Meanwhile, there was a substantial increase in the expression of P53 and BAX, BCL2 was significantly down-regulated. On the contrary, interfering with YTHDF2 increased cell proliferation and reduced cell apoptosis. Furthermore, YTHDF2 overexpression exacerbated the decrease in cell viability under BkF exposure, while YTHDF2 knockdown was the opposite. The results from the RIP assay demonstrated a significant enhancement in the interaction of YTHDF2 protein with BCL2 mRNA following the overexpression of YTHDF2. In addition, animal experiments showed that there was an increase in apoptosis and a decrease in proliferation of testicular cells in mice in the high-dose (30 mg/kg) BkF group by TUNEL staining and Ki67 staining. Immunohistochemical analysis showed that BCL2 levels were significantly lower in the high-dose group than in the control group, while YTHDF2, P53 and BAX were dramatically increased. In summary, our study suggests that YTHDF2 has been implicated in BkF-induced male reproductive injury by promoting the degradation of BCL2.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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