PMID- 29540747
OWN - NLM
STAT- MEDLINE
DCOM- 20190930
LR  - 20211204
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 8
IP  - 1
DP  - 2018 Mar 14
TI  - Bone marrow mesenchymal stem cells protect against n-hexane-induced neuropathy 
      through beclin 1-independent inhibition of autophagy.
PG  - 4516
LID - 10.1038/s41598-018-22857-x [doi]
LID - 4516
AB  - Chronic exposure to n-hexane, a widely used organic solvent in industry, induces 
      central-peripheral neuropathy, which is mediated by its active metabolite, 
      2,5-hexanedione (HD). We recently reported that transplantation of bone 
      marrow-mesenchymal stem cells (BMSC) significantly ameliorated HD-induced 
      neuronal damage and motor deficits in rats. However, the mechanisms remain 
      unclear. Here, we reported that inhibition of HD-induced autophagy contributed to 
      BMSC-afforded protection. BMSC transplantation significantly reduced the levels 
      of microtubule-associated protein 1 light chain 3-II (LC3-II) and the degradation 
      of sequestosome-1 (p62) in the spinal cord and sciatic nerve of HD-intoxicated 
      rats. Downregulation of autophagy by BMSC was also confirmed in VSC4.1 cells 
      exposed to HD. Moreover, inhibition of autophagy by PIK III mitigated the 
      neurotoxic effects of HD and, meanwhile, abolished BMSC-afforded neuroprotection. 
      Furthermore, we found that BMSC failed to interfere with Beclin 1, but promoted 
      activation of mammalian target of rapamycin (mTOR). Unc-like kinse 1 (ULK1) was 
      further recognized as the downstream target of mTOR responsible for BMSC-mediated 
      inhibition of autophagy. Altogether, BMSC transplantation potently ameliorated 
      HD-induced autophagy through beclin 1-independent activation of mTOR pathway, 
      providing a novel insight for the therapeutic effects of BMSC against n-hexane 
      and other environmental toxicants-induced neurotoxicity.
FAU - Hao, Jie
AU  - Hao J
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Li, Shuangyue
AU  - Li S
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Shi, Xiaoxia
AU  - Shi X
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Qian, Zhiqiang
AU  - Qian Z
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Sun, Yijie
AU  - Sun Y
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Wang, Dunjia
AU  - Wang D
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Zhou, Xueying
AU  - Zhou X
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Qu, Hongxin
AU  - Qu H
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Hu, Shuhai
AU  - Hu S
AD  - College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, 
      China.
FAU - Zuo, Enjun
AU  - Zuo E
AD  - College of Stomatology, Dalian Medical University, Dalian, Liaoning, 116044, 
      China.
FAU - Zhang, Cong
AU  - Zhang C
AD  - Department of Nutrition and Food Safety, Dalian Medical University, Dalian, 
      Liaoning, 116044, China.
FAU - Hou, Liyan
AU  - Hou L
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China.
FAU - Wang, Qingshan
AU  - Wang Q
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China. wangq4@126.com.
FAU - Piao, Fengyuan
AU  - Piao F
AD  - Department of Occupational and Environmental Health, Dalian Medical University, 
      Dalian, Liaoning, 116044, China. piaofengyuan353@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180314
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Beclin-1)
RN  - 0 (Hexanes)
RN  - 2DDG612ED8 (n-hexane)
RN  - 9061-61-4 (Nerve Growth Factor)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - Autophagy/*drug effects/*genetics
MH  - Beclin-1/*genetics/metabolism
MH  - Cell Communication
MH  - Gene Expression
MH  - Hexanes/*adverse effects
MH  - *Mesenchymal Stem Cell Transplantation
MH  - Mesenchymal Stem Cells/cytology/*metabolism
MH  - Nerve Growth Factor/pharmacology
MH  - Neurons/drug effects/metabolism
MH  - Neuroprotection
MH  - Peripheral Nervous System Diseases/*etiology/*metabolism/physiopathology/therapy
MH  - Rats
MH  - TOR Serine-Threonine Kinases/metabolism
PMC - PMC5852116
COIS- The authors declare no competing interests.
EDAT- 2018/03/16 06:00
MHDA- 2019/10/01 06:00
PMCR- 2018/03/14
CRDT- 2018/03/16 06:00
PHST- 2017/07/26 00:00 [received]
PHST- 2018/02/13 00:00 [accepted]
PHST- 2018/03/16 06:00 [entrez]
PHST- 2018/03/16 06:00 [pubmed]
PHST- 2019/10/01 06:00 [medline]
PHST- 2018/03/14 00:00 [pmc-release]
AID - 10.1038/s41598-018-22857-x [pii]
AID - 22857 [pii]
AID - 10.1038/s41598-018-22857-x [doi]
PST - epublish
SO  - Sci Rep. 2018 Mar 14;8(1):4516. doi: 10.1038/s41598-018-22857-x.