PMID- 29396411
OWN - NLM
STAT- MEDLINE
DCOM- 20190802
LR  - 20211204
IS  - 2041-4889 (Electronic)
VI  - 9
IP  - 2
DP  - 2018 Feb 2
TI  - Clinorotation-induced autophagy via HDM2-p53-mTOR pathway enhances cell migration 
      in vascular endothelial cells.
PG  - 147
LID - 10.1038/s41419-017-0185-2 [doi]
LID - 147
AB  - Individuals exposed to long-term spaceflight often experience cardiovascular 
      dysfunctions characterized by orthostatic intolerance, disability on physical 
      exercise, and even frank syncope. Recent studies have showed that the alterations 
      of cardiovascular system are closely related to the functional changes of 
      endothelial cells. We have shown previously that autophagy can be induced by 
      simulated microgravity in human umbilical vein endothelial cells (HUVECs). 
      However, the mechanism of enhanced autophagy induced by simulated microgravity 
      and its role in the regulation of endothelial function still remain unclear. We 
      report here that 48 h clinorotation promoted cell migration in HUVECs by 
      induction of autophagy. Furthermore, clinorotation enhanced autophagy by the 
      mechanism of human murine double minute 2 (HDM2)-dependent degradation of 
      cytoplasmic p53 at 26S proteasome, which results in the suppression of 
      mechanistic target of rapamycin (mTOR), but not via activation of AMPK in HUVECs. 
      These results support the key role of HDM2-p53 in direct downregulation of mTOR, 
      but not through AMPK in microgravity-induced autophagy in HUVECs.
FAU - Li, Cheng-Fei
AU  - Li CF
AD  - Department of Aerospace Biodynamics, School of Aerospace Medicine, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Sun, Jia-Xing
AU  - Sun JX
AD  - Key lab of Aerospace Medicine, Chinese Ministry of Education, Xi'an, Shaanxi, 
      710032, China.
FAU - Gao, Yuan
AU  - Gao Y
AD  - Department of Aerospace Biodynamics, School of Aerospace Medicine, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Shi, Fei
AU  - Shi F
AD  - Department of Aerospace Biodynamics, School of Aerospace Medicine, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Pan, Yi-Kai
AU  - Pan YK
AD  - Department of Aerospace Biodynamics, School of Aerospace Medicine, Fourth 
      Military Medical University, Xi'an, 710032, China.
FAU - Wang, Yong-Chun
AU  - Wang YC
AD  - Key lab of Aerospace Medicine, Chinese Ministry of Education, Xi'an, Shaanxi, 
      710032, China. wangych@fmmu.edu.cn.
FAU - Sun, Xi-Qing
AU  - Sun XQ
AD  - Department of Aerospace Biodynamics, School of Aerospace Medicine, Fourth 
      Military Medical University, Xi'an, 710032, China. sunxiqing@fmmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180202
PL  - England
TA  - Cell Death Dis
JT  - Cell death & disease
JID - 101524092
RN  - 0 (Fatty Acids, Unsaturated)
RN  - 0 (Leupeptins)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Suppressor Protein p53)
RN  - EC 2.3.2.27 (MDM2 protein, human)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-mdm2)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - RF1P63GW3K (benzyloxycarbonylleucyl-leucyl-leucine aldehyde)
RN  - Y031I2N1EO (leptomycin B)
MH  - AMP-Activated Protein Kinases/metabolism
MH  - *Autophagy/drug effects
MH  - *Cell Movement/drug effects
MH  - Fatty Acids, Unsaturated/pharmacology
MH  - Gene Knockdown Techniques
MH  - Human Umbilical Vein Endothelial Cells/*cytology/*metabolism/ultrastructure
MH  - Humans
MH  - Leupeptins/pharmacology
MH  - Models, Biological
MH  - Phosphorylation/drug effects
MH  - Proteasome Endopeptidase Complex/metabolism
MH  - Proteolysis/drug effects
MH  - Proto-Oncogene Proteins c-mdm2/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - *Rotation
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*metabolism
MH  - Time Factors
MH  - Tumor Suppressor Protein p53/*metabolism
MH  - Weightlessness Simulation
PMC - PMC5833810
COIS- The authors declare that they have no conflict of interest.
EDAT- 2018/02/06 06:00
MHDA- 2019/08/03 06:00
PMCR- 2018/02/02
CRDT- 2018/02/04 06:00
PHST- 2017/07/25 00:00 [received]
PHST- 2017/11/27 00:00 [accepted]
PHST- 2017/11/14 00:00 [revised]
PHST- 2018/02/04 06:00 [entrez]
PHST- 2018/02/06 06:00 [pubmed]
PHST- 2019/08/03 06:00 [medline]
PHST- 2018/02/02 00:00 [pmc-release]
AID - 10.1038/s41419-017-0185-2 [pii]
AID - 185 [pii]
AID - 10.1038/s41419-017-0185-2 [doi]
PST - epublish
SO  - Cell Death Dis. 2018 Feb 2;9(2):147. doi: 10.1038/s41419-017-0185-2.