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Aroclor1254 disrupts the blood–testis barrier by promoting endocytosis and degradation of junction proteins via p38 MAPK pathway
- Source :
- Cell Death & Disease
- Publication Year :
- 2017
- Publisher :
- Springer Science and Business Media LLC, 2017.
-
Abstract
- The blood–testis barrier (BTB) constituted by coexisting junction apparatus between Sertoli cells (SCs) plays an important role in spermatogenesis, which is a known target of various environmental toxicants. The commercial polychlorinated biphenyls mixture, Aroclor1254, has been shown to impair male reproduction by decreasing sperm count and affecting SC metabolism. This study was designed to investigate the effects of Aroclor1254 on the BTB integrity and elucidate the underlying mechanisms. We found that Aroclor1254 treatment in rats (1 or 3 mg/kg per day for 21 consecutive days) and in primary cultured SCs (5 or 10 μg/ml for 48 h) could induce BTB disruption via p38 MAPK pathway, concurrently with increments in junction proteins (JAM-A, N-cadherin, and β-catenin) endocytosis, and occludin ubiquitination. Either inhibition of caveolin-dependent membrane protein internalization by cholesterol oxidase or silencing E3 ubiquitine ligase Itch by small interfering RNA could partially counteract the effects of Aroclor1254 on the barrier function of cultured SCs. These results demonstrate that Aroclor1254 disrupts the BTB function by promoting the caveolin-dependent endocytosis and ubiquitine–proteasome degradation of junction proteins through the p38 MAPK pathway, which might be the potential reasons for its negative effects on spermatogenesis and male reproduction.
- Subjects :
- Male
0301 basic medicine
Cancer Research
Small interfering RNA
MAP Kinase Signaling System
Ubiquitin-Protein Ligases
media_common.quotation_subject
Immunology
Biology
Endocytosis
Occludin
p38 Mitogen-Activated Protein Kinases
Epithelium
Rats, Sprague-Dawley
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
medicine
Animals
Internalization
Blood-Testis Barrier
Cells, Cultured
Barrier function
Blood–testis barrier
media_common
Sertoli Cells
Tight Junction Proteins
Ubiquitination
Cell Biology
Chlorodiphenyl (54% Chlorine)
Sertoli cell
Cell biology
030104 developmental biology
medicine.anatomical_structure
Membrane protein
Gene Knockdown Techniques
030220 oncology & carcinogenesis
Proteolysis
Original Article
Subjects
Details
- ISSN :
- 20414889
- Volume :
- 8
- Database :
- OpenAIRE
- Journal :
- Cell Death & Disease
- Accession number :
- edsair.doi.dedup.....50f805c749ac3ea78e332654cfed2493