Back to Search
Start Over
4-Nonylphenol induces autophagy and attenuates mTOR-p70S6K/4EBP1 signaling by modulating AMPK activation in Sertoli cells
- Publication Year :
- 2017
- Publisher :
- Elsevier, 2017.
-
Abstract
- The estrogenic chemical 4-nonylphenol (NP) is known to impair testicular devolopment and spermatogenesis in rodents. The objective of this study was to explore the effects of NP on autophagy induction and AMPK-mTOR signaling pathway in Sertoli cells (SCs), which are the “nursemaid cells” for meiosis of spermatocytes. In this study we exposed 7-week-old male rats to NP by intra-peritoneal injection at 0, 20, 50 or 100 mg/kg body weight/2 days for 20 consecutive days. Our results showed that exposure to NP dose-dependently induces the formation of autophagosomes in SCs, increases the expression of Beclin-1, the conversion of LC3-I to LC3-II and the mRNA expression of Atg3, Atg5, Atg7 and Atg12 in testis, and these effects are concomitant with the activation of AMPK, and the suppression of TSC2-mTOR-p70S6K/4EBP1 signaling cascade in testis. Furthermore, 10 µM Compound C or AMPKα1 siRNA pre-treatment effectively attenuated autophagy and reversed AMPK-mTOR-p70S6K/4EBP1 signaling in NP-treated SCs. Co-treatment with 1 mM AICAR remarkably strengthened NP-induced autophagy and mTOR inhibition in SCs. Together, these data suggest that NP stimulates Sertoli cell autophagy and inhibits mTOR-p70S6K/4EBP1 activity through AMPK activation, which is the potential mechanism responsible for the regulation of testis function and differentiation following NP exposure.
- Subjects :
- 0301 basic medicine
Male
Time Factors
ATG5
B220
Enzyme Activators
Biology
AMP-Activated Protein Kinases
Endocrine Disruptors
Toxicology
Transfection
ATG12
Rats, Sprague-Dawley
03 medical and health sciences
0302 clinical medicine
AMP-activated protein kinase
Phenols
medicine
Autophagy
Animals
Phosphorylation
RNA, Small Interfering
Protein Kinase Inhibitors
PI3K/AKT/mTOR pathway
Cells, Cultured
Sertoli Cells
Dose-Response Relationship, Drug
C142
TOR Serine-Threonine Kinases
B131
Intracellular Signaling Peptides and Proteins
AMPK
Ribosomal Protein S6 Kinases, 70-kDa
Estrogens
General Medicine
Sertoli cell
Phosphoproteins
Cell biology
Enzyme Activation
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
biology.protein
RNA Interference
Signal transduction
Carrier Proteins
Signal Transduction
Subjects
Details
- Language :
- English
- ISSN :
- 03784274
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....064a8788fc1d4e25c889790d3f861ccf