Inhibition of autophagy in theca cells induces CYP17A1 and PAI-1 expression via ROS/p38 and JNK signalling during the development of polycystic ovary syndrome.
Adult
Animals
Autophagy
/ drug effects
Cattle
Chloroquine
/ pharmacology
Female
Humans
MAP Kinase Signaling System
/ drug effects
Mitochondria
/ drug effects
Palmitic Acid
/ pharmacology
Plasminogen Activator Inhibitor 1
/ genetics
Polycystic Ovary Syndrome
/ genetics
RNA, Messenger
/ genetics
Reactive Oxygen Species
/ metabolism
Sequestosome-1 Protein
/ metabolism
Steroid 17-alpha-Hydroxylase
/ genetics
Theca Cells
/ metabolism
Ubiquitin
/ metabolism
Up-Regulation
/ drug effects
p38 Mitogen-Activated Protein Kinases
/ metabolism
Autophagy
CYP17A1
PAI-1
PCOS
Theca cell
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 05 2020
15 05 2020
Historique:
received:
11
11
2019
revised:
12
03
2020
accepted:
12
03
2020
pubmed:
23
3
2020
medline:
28
5
2021
entrez:
23
3
2020
Statut:
ppublish
Résumé
Polycystic ovary syndrome (PCOS) is a clinical syndrome characterized by hyperandrogenism, oligo/anovulation, and polycystic ovary. Autophagy is an intracellular system that degrades cytosolic proteins and organelles. The relationship between autophagy and PCOS has not been clarified. We found that p62 and ubiquitin were significantly increased in theca cells of women with PCOS using immunohistochemistry. Autophagy inhibition by palmitic acid and chloroquine in bovine theca cells increased p62 and ubiquitin and induced the expression of cytochrome P450 17A1 (CYP17A1) and plasminogen activator inhibitor-1 (PAI-1) mRNA. Furthermore, palmitic acid and chloroquine exposure significantly increased reactive oxygen species (ROS) and activated p38 and c-Jun N-terminal kinase (JNK). Inhibition of p38 and JNK significantly reduced CYP17A1 and PAI-1 mRNA expression. We showed that inhibition of autophagy in theca cells may have contributed to the pathogenesis of PCOS, based on CYP17A1 and PAI-1 mRNA expression via the ROS/p38 and JNK signalling pathways.
Identifiants
pubmed: 32199904
pii: S0303-7207(20)30092-7
doi: 10.1016/j.mce.2020.110792
pii:
doi:
Substances chimiques
Plasminogen Activator Inhibitor 1
0
RNA, Messenger
0
Reactive Oxygen Species
0
SQSTM1 protein, human
0
Sequestosome-1 Protein
0
Ubiquitin
0
Palmitic Acid
2V16EO95H1
Chloroquine
886U3H6UFF
Steroid 17-alpha-Hydroxylase
EC 1.14.14.19
p38 Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110792Informations de copyright
Copyright © 2020 Elsevier B.V. All rights reserved.