TERT transcription and translocation into mitochondria regulate benzo[a]pyrene/BPDE-induced senescence and mitochondrial damage in mouse spermatocytes.
Benzo[a]Pyrene
Benzo[a]Pyrene-7,8-Dihydrodiol-9,10-Epoxide
Mitochondrial Damage
Spermatocyte
Telomere Dysfunction
Telomeric Reverse Transcriptase
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 09 2023
15 09 2023
Historique:
received:
04
03
2023
revised:
07
08
2023
accepted:
11
08
2023
medline:
28
8
2023
pubmed:
15
8
2023
entrez:
14
8
2023
Statut:
ppublish
Résumé
Telomere and mitochondria may be the targets of Benzo[a]pyrene (BaP) -induced male reproductive damage, and further elucidation of the toxic molecular mechanisms is necessary. In this study, we used in vivo and in vitro exposure models to explore the molecular mechanisms of TERT regulation in BaP-induced telomere and mitochondrial damage in spermatocytes. The results showed that the treatment of benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (BPDE), the active metabolite of BaP, caused telomere dysfunction in mouse spermatocyte-derived GC-2 cells, resulting in S-phase arrest and increased senescence-associated secretory phenotype (SASP). These effects were significantly alleviated by telomerase agonist (ABG) pretreatment in GC-2 cells. SIRT1, FOXO3a, or c-MYC overexpressing GC-2 cell models were established to demonstrate that BPDE inhibited TERT transcriptional expression through the SIRT1/FOXO3a/c-MYC pathway, leading to telomere dysfunction. We also observed that BPDE induced mitochondrial compromise, including complex I damage, accompanied by reduced mitochondrial TERT expression. Based on this, we constructed wild-type TERT-overexpressing (OE-TERT
Identifiants
pubmed: 37579952
pii: S0041-008X(23)00295-8
doi: 10.1016/j.taap.2023.116656
pii:
doi:
Substances chimiques
Benzo(a)pyrene
3417WMA06D
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide
55097-80-8
Sirtuin 1
EC 3.5.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
116656Informations de copyright
Copyright © 2023. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
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. The following are the supplementary data related to this article. Supplementary data to this article can be found online at https://doi.org/10.1016/j.taap.2023.116656.