PMID- 29961786
OWN - NLM
STAT- MEDLINE
DCOM- 20190816
LR  - 20211204
IS  - 1756-591X (Electronic)
IS  - 1756-5901 (Linking)
VI  - 10
IP  - 7
DP  - 2018 Jul 18
TI  - Selenoprotein-U (SelU) knockdown triggers autophagy through PI3K-Akt-mTOR pathway 
      inhibition in rooster Sertoli cells.
PG  - 929-940
LID - 10.1039/c8mt00090e [doi]
AB  - Selenium (Se) is a major component of male reproduction which exerts its effects 
      via selenoproteins. Selenoprotein U (SelU), a newly identified protein, is 
      expressed highly in eukaryotes and possesses a conserved motif similar to that 
      existing in other thiol-dependent redox regulating selenoproteins; however its 
      function is unknown. To investigate the role of SelU in testis autophagic and/or 
      apoptosis cell death mechanisms, we established a Sertoli cell (SC) model 
      isolated from 45 day old layer roosters. Small interfering RNA (siRNA) technology 
      was used to develop SelU-knockdown (SelU-KD) and normal (N) SC models. Consequent 
      to transfection, electron microscopy, qPCR, and western blot were performed. The 
      results show that the mRNA and proteins of autophagy and anti-apoptosis genes 
      increased while that of anti-autophagic mammalian target of rapamycin (mTOR) and 
      pro-apoptosis genes decreased significantly in SelU-KD in contrast to N cells. 
      Simultaneously, in contrast to N cells the expression of 
      phosphoinositide-3-kinase (PI3K) and protein kinase B (PKB/Akt) both at the mRNA 
      and protein levels decreased significantly in SelU-KD cells. In-addition, SelU 
      depletion altered the expression of regulatory factors and increased the mRNA of 
      TSC (tuberous sclerosis complex) genes as compared to N cells. Extensive 
      autophagosome formation and lysosome degradation with an intact cytoskeleton were 
      observed in SelU-KD cells. Our data indicate that SelU deprivation elicits 
      autophagy and reduces the expression of important growth factors in SCs by 
      disrupting the PI3K-Akt-mTOR signaling pathway. However SelU attenuation did not 
      induce apoptosis in rooster SCs. Taken together, we conclude that SelU is 
      essential for the survival and normal functioning of SCs.
FAU - Sattar, Hamid
AU  - Sattar H
AD  - College of Veterinary Medicine, Northeast Agricultural University, 59 Mucai 
      Street, Harbin 150030, P. R. China. shiwenxu@neau.edu.cn zhangziwei@neau.edu.cn.
FAU - Yang, Jie
AU  - Yang J
FAU - Zhao, Xia
AU  - Zhao X
FAU - Cai, Jingzeng
AU  - Cai J
FAU - Liu, Qi
AU  - Liu Q
FAU - Ishfaq, Muhammad
AU  - Ishfaq M
FAU - Yang, Zijiang
AU  - Yang Z
FAU - Chen, Menghao
AU  - Chen M
FAU - Zhang, Ziwei
AU  - Zhang Z
FAU - Xu, Shiwen
AU  - Xu S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Metallomics
JT  - Metallomics : integrated biometal science
JID - 101478346
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Selenoproteins)
RN  - EC 2.7.1.137 (Phosphatidylinositol 3-Kinase)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
MH  - Animals
MH  - *Apoptosis
MH  - *Autophagy
MH  - Cell Proliferation
MH  - Cells, Cultured
MH  - Chickens
MH  - Male
MH  - Phosphatidylinositol 3-Kinase/genetics/metabolism
MH  - *Phosphoinositide-3 Kinase Inhibitors
MH  - Proto-Oncogene Proteins c-akt/*antagonists & inhibitors/genetics/metabolism
MH  - RNA, Small Interfering/genetics
MH  - Selenoproteins/*antagonists & inhibitors/genetics/metabolism
MH  - Sertoli Cells/metabolism/*pathology
MH  - Signal Transduction
MH  - Spermatogenesis
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors/genetics/metabolism
EDAT- 2018/07/03 06:00
MHDA- 2019/08/17 06:00
CRDT- 2018/07/03 06:00
PHST- 2018/07/03 06:00 [pubmed]
PHST- 2019/08/17 06:00 [medline]
PHST- 2018/07/03 06:00 [entrez]
AID - 10.1039/c8mt00090e [doi]
PST - ppublish
SO  - Metallomics. 2018 Jul 18;10(7):929-940. doi: 10.1039/c8mt00090e.