PMID- 29510402
OWN - NLM
STAT- MEDLINE
DCOM- 20180514
LR  - 20211204
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 45
IP  - 5
DP  - 2018
TI  - Oxymatrine Inhibits Homocysteine-Mediated Autophagy via MIF/mTOR Signaling in 
      Human Umbilical Vein Endothelial Cells.
PG  - 1893-1903
LID - 10.1159/000487912 [doi]
AB  - BACKGROUND/AIMS: Genetic or nutritional deficiencies in homocysteine 
      (Hcy)metabolism lead to the accumulation of Hcy and its metabolites in the blood. 
      This can lead to hyperhomocysteinemia (HHcy), which is an independent risk factor 
      for cardiovascular disease. Studies have shown that HHcy leads to endothelial 
      dysfunction, a hallmark of atherosclerosis, which may explain this link. The 
      precise mechanism remains unclear, but a strong possibility is excessive 
      HHCy-induced autophagy. Autophagy has been better studied in ischemia/reperfusion 
      (I/R) injuries, and previous work showed that Oxymatrine (OMT), a quinolizidine 
      alkaloid, protects cells against myocardial I/R injury by inhibiting autophagy. 
      The aim of this study was to determine whether OMT inhibits autophagy in HHcy. 
      METHODS: Autophagy in HUVEC cells treated with Hcy in the presence and absence of 
      OMT was visualized bytransmission electron microscopy and the degree was 
      determined by western blotting and qRT-PCR. Small interfering RNA (siRNA)was used 
      to determine the efficiency of Macrophage migration inhibitory factor (MIF) 
      inhibition. Cell apoptosis wasdetected by western blotting and flow cytometric 
      analysis. RESULTS: OMT inhibited autophagy, MIF, and mTOR in HUVECs during Hcy 
      exposure, depending on the dose. siRNA-mediated MIF knockdown decreased 
      Hcy-induced autophagy, while administration of 3-methyladenosine and rapamycin 
      showed that they also induce autophagy. Furthermore, OMT dose-dependently 
      inhibited the Hcy-induced HUVEC apoptosis/death. CONCLUSIONS: These results 
      suggest that Hcy can evokeautophagy-activated HUVEC apoptosis/death via a 
      MIF/mTOR signaling pathway, which can be reversed by OMT. Our results provide a 
      new insight into a functional role of OMT in the prevention of Hcy-induced HUVEC 
      injury and death.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Zhang, Yanyan
AU  - Zhang Y
AD  - Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou 
      Medical University, Guizhou, China.
FAU - Zhang, Yuan
AU  - Zhang Y
AD  - Department of Neurology, Xiangya Hospital, Central South University, Changsha, 
      China.
AD  - Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Tang, Jiayu
AU  - Tang J
AD  - Department of Neurology, Brain Hospital of Hunan Province, Changsha, China.
FAU - Zhao, Shuang
AU  - Zhao S
AD  - Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou 
      Medical University, Guizhou, China.
FAU - Li, Chen
AU  - Li C
AD  - Key Laboratory of Optimal Utilization of Natural Medicine Resources, Guizhou 
      Medical University, Guizhou, China.
FAU - Huang, Yong-Pan
AU  - Huang YP
AD  - Department of Pharmacology, Institute of Chinese Medicine, Hunan Academy of 
      Chinese Medicine, Changsha, China.
FAU - Yi, Minhan
AU  - Yi M
AD  - Information Security and Big Data Research Institute & School of Life Sciences, 
      Central South University, Changsha, China.
AD  - Department of Ecology and Evolutionary Biology, University of Michigan, Ann 
      Arbor, Michigan, USA.
LA  - eng
PT  - Journal Article
DEP - 20180228
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (Alkaloids)
RN  - 0 (MAP1LC3A protein, human)
RN  - 0 (Macrophage Migration-Inhibitory Factors)
RN  - 0 (Microtubule-Associated Proteins)
RN  - 0 (Quinolizines)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (SQSTM1 protein, human)
RN  - 0 (Sequestosome-1 Protein)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 72055-62-0 (3-methyladenosine)
RN  - 85U4C366QS (oxymatrine)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 5.3.- (Intramolecular Oxidoreductases)
RN  - EC 5.3.2.1 (MIF protein, human)
RN  - K72T3FS567 (Adenosine)
RN  - W36ZG6FT64 (Sirolimus)
SB  - IM
MH  - Adenosine/analogs & derivatives/pharmacology
MH  - Alkaloids/*pharmacology
MH  - Apoptosis/drug effects
MH  - Autophagy/*drug effects
MH  - Caspase 3/metabolism
MH  - Homocysteine/*toxicity
MH  - Human Umbilical Vein Endothelial Cells
MH  - Humans
MH  - Intramolecular Oxidoreductases/antagonists & inhibitors/genetics/*metabolism
MH  - Macrophage Migration-Inhibitory Factors/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Microscopy, Electron, Transmission
MH  - Microtubule-Associated Proteins/metabolism
MH  - Quinolizines/*pharmacology
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - Sequestosome-1 Protein/metabolism
MH  - Signal Transduction/*drug effects
MH  - Sirolimus/pharmacology
MH  - TOR Serine-Threonine Kinases/antagonists & inhibitors/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Autophagy
OT  - HUVECs
OT  - Homocysteine
OT  - Oxymatrine
EDAT- 2018/03/07 06:00
MHDA- 2018/05/15 06:00
CRDT- 2018/03/07 06:00
PHST- 2017/04/04 00:00 [received]
PHST- 2018/01/26 00:00 [accepted]
PHST- 2018/03/07 06:00 [pubmed]
PHST- 2018/05/15 06:00 [medline]
PHST- 2018/03/07 06:00 [entrez]
AID - 000487912 [pii]
AID - 10.1159/000487912 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;45(5):1893-1903. doi: 10.1159/000487912. Epub 2018 Feb 
      28.