Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 391, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2020.122227
Keywords
Arsenic; Autophagy; MTOR pathway; Beclin1-Vps34/PI3K complex; Male reproductive toxicity
Categories
Funding
- National Natural Science Foundation of China [31741120]
- Natural Science Foundation of Shanxi Province [201901D111233]
- Top Youth Talent Plan of Shanxi Province
- Key Science Research and Development Project of Shanxi Province [201903D211008]
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Arsenic poisoning and induced potential lesion is a global concern. However, the exact mechanisms underlying its toxicity especially in male reproductive system still remain unclear. Hence, this study aimed to explore the roles of mTOR and Beclin1-Vps34/PI3K complex during As-induced-toxicity using Rapamycin (mTOR inhibitor), Beclin1 siRNA and 3-methyladenine (3-MA, Vps34/PI3K inhibitor) in testicular stromal cells. For this, mouse testis Leydig Tumor Cell lines (MLTC-1) were challenged with As2O3 (0, 3, 6 and 9 mu M) exposure for 24 hs. LysoTracker Red and Monodansylcadaverine (MDC) staining results depicted a significant accumulation of autophagosomes in MLTC-1 cells exposed to arsenic. Meanwhile, arsenic treatment up-regulated autophagic markers including LC3, Atg7, Beclin1 and Vps34 expressions, mTOR downstream autophagy related genes and the Beclin1-Vps34/PI3K complex associated members. Furthermore, silencing of Beclin1, and inhibition of Vps34/ PI3K and mTOR altered the arsenic-induced autophagosomes formation. However, p62, the substrate protein of autophagy, was also up-regulated by arsenic administration independent on Beclin1-Vps34/PI3K complex. Altogether, our results revealed that arsenic exposure induced autophagosomes formation via regulation of the Beclin1-Vps34/PI3K complex and mTOR pathway; the blockage of autophagosomes degradation maybe due to impaired function of lysosomes. Thus, this study provides a novel mechanistic approach with respect to Asinduced male reproductive toxicity.
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