Upregulated Autophagy in Sertoli Cells of Ethanol-Treated Rats Is Associated with Induction of Inducible Nitric Oxide Synthase (iNOS), Androgen Receptor Suppression and Germ Cell Apoptosis

International Journal of Molecular Sciences
Akio HoribeYoichi Kondo

Abstract

This study was conducted to investigate the autophagic response of Sertoli cells (SCs) to acute ethanol toxicity using in vivo and in vitro models. Adult Wistar rats were intraperitoneally injected with either 5 g/kg ethanol or phosphate-buffered saline (for the control group) and sacrificed 0, 3, 6 and 24 h after injection. Compared to the control group, enhanced germ cell apoptosis was observed in the ethanol-treated rats (ETRs) in association with upregulation of iNOS and reduced expression of androgen receptor protein levels in SCs, which were resistant to apoptosis. Meanwhile, autophagy was upregulated in ETR SCs (peaking at 24 h) compared to the control group, as evidenced by transcription factor EB (TFEB) nuclear translocation, enhanced expression of microtubule-associated protein 1 light chain3-II (LC3-II), lysosome-associated membrane protein-2 (LAMP-2), pan cathepsin protein levels and reduced expression of p62. This upregulation of SC autophagy was confirmed ultrastructurally by enhanced formation of autophagic vacuoles and by immunofluorescent double labelling of autophagosomal and lysosomal markers. Study of cultured SCs confirmed enhanced autophagic response to ethanol toxicity, which was cytoprotective based on d...Continue Reading

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Citations

May 28, 2019·Bioscience Reports·Fukai WangZhiyong Yu
Jul 29, 2020·Andrologia·Nareelak Tangsrisakda, Sitthichai Iamsaard
Feb 23, 2020·Frontiers in Pharmacology·Nabil EidErnest Adeghate
Sep 28, 2017·Scientific Reports·Lin WangXiao-Ming Yin

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Methods Mentioned

BETA
nuclear translocation
transmission electron microscopy
Assay

Software Mentioned

GraphPad
PRISM
Image J

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