PCB153 reduces apoptosis in primary cultures of murine pituitary cells through the activation of NF-κB mediated by PI3K/Akt.
Animals
Apoptosis
/ drug effects
Caspase 3
/ metabolism
Cell Proliferation
/ drug effects
Cells, Cultured
Cyclin-Dependent Kinase Inhibitor p21
/ metabolism
Male
Mice, Inbred C57BL
Mitochondria
/ drug effects
NF-kappa B
/ metabolism
Phosphatidylinositol 3-Kinases
/ metabolism
Pituitary Gland
/ metabolism
Polychlorinated Biphenyls
/ toxicity
Proto-Oncogene Proteins c-akt
/ metabolism
Receptors, Death Domain
/ metabolism
Signal Transduction
/ drug effects
Tumor Suppressor Protein p53
/ metabolism
Apoptosis
NF-κB
PCB153
PI3K/Akt
Pituitary
p21/p53
Journal
Molecular and cellular endocrinology
ISSN: 1872-8057
Titre abrégé: Mol Cell Endocrinol
Pays: Ireland
ID NLM: 7500844
Informations de publication
Date de publication:
15 01 2021
15 01 2021
Historique:
received:
29
08
2019
revised:
02
11
2020
accepted:
17
11
2020
pubmed:
27
11
2020
medline:
13
8
2021
entrez:
26
11
2020
Statut:
ppublish
Résumé
Polychlorinated biphenyls (PCBs) are persistent pollutants involved in human tumorigenesis. PCB153 is a ubiquitous non-dioxin-like PCB with proliferative and anti-apoptotic effects. To explore the impact of PCB153 in the survival of pituitary cells, we exposed murine pituitary primary cells to PCB153 10 μM for 24 h. Apoptosis was assessed by RT-qPCR, Western-blot, immunoprecipitation, caspase activity, and immunofluorescence. We found that PCB153 decreased pituitary apoptosis through both the extrinsic and intrinsic pathways. PCB153 reduced the level of the pro-apoptotic protein p38-MAPK. Otherwise, PCB153 activated PI3K/Akt and Erk1/2 pathways and enhanced the expression and nuclear translocation of NF-κB. Cotreatments with specific inhibitors revealed that only PI3K/Akt changed the caspase-3 expression and NF-κB activation induced by PCB153. Also, PCB153 decreased the expression of the pro-apoptotic and pro-senescent cyclins p53 and p21. In summary, exposure to PCB153 leads to a downregulation of apoptosis in the pituitary driven by a PI3K/Akt-mediated activation of NF-κB.
Identifiants
pubmed: 33242503
pii: S0303-7207(20)30392-0
doi: 10.1016/j.mce.2020.111090
pii:
doi:
Substances chimiques
Cyclin-Dependent Kinase Inhibitor p21
0
NF-kappa B
0
Receptors, Death Domain
0
Tumor Suppressor Protein p53
0
Polychlorinated Biphenyls
DFC2HB4I0K
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Caspase 3
EC 3.4.22.-
2,4,5,2',4',5'-hexachlorobiphenyl
ZRU0C9E32O
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
111090Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.