PMID- 27185663
OWN - NLM
STAT- MEDLINE
DCOM- 20170605
LR  - 20220129
IS  - 1879-3649 (Electronic)
IS  - 1537-1891 (Print)
IS  - 1537-1891 (Linking)
VI  - 83
DP  - 2016 Aug
TI  - Increased aerobic glycolysis is important for the motility of activated VSMC and 
      inhibited by indirubin-3'-monoxime.
PG  - 47-56
LID - S1537-1891(15)30107-5 [pii]
LID - 10.1016/j.vph.2016.05.002 [doi]
AB  - Increased aerobic glycolysis is a recognized feature of multiple cellular 
      phenotypes and offers a potential point for drug interference, as pursued by 
      anti-tumor agents targeting the Warburg effect. This study aimed at examining the 
      role of aerobic glycolysis for migration of vascular smooth muscle cells (VSMC) 
      and its susceptibility to the small molecule indirubin-3'-monoxime (I3MO). 
      Activation of VSMC with platelet-derived growth factor (PDGF) resulted in 
      migration and increased glycolytic activity which was accompanied by an increased 
      glucose uptake and hexokinase (HK) 2 expression. Inhibition of glycolysis or 
      hexokinase by pharmacological agents or siRNA-mediated knockdown significantly 
      reduced the migratory behavior in VSMC without affecting cell viability or early 
      actin cytoskeleton rearrangement. I3MO, previously recognized as inhibitor of 
      VSMC migration, was able to counteract the PDGF-activated increase in glycolysis 
      and HK2 abundance. Activation of signal transducer and activator of transcription 
      (STAT) 3 could be identified as crucial event in upregulation of HK2 and 
      glycolytic activity in PDGF-stimulated VSMC and as point of interference for 
      I3MO. I3MO did not inhibit hypoxia-inducible factor (HIF)1alpha-dependent 
      transcription nor influence miRNA 143 levels, other potential regulators of HK2 
      levels. Overall, we demonstrate that increased aerobic glycolysis is an important 
      factor for the motility of activated VSMC and that the anti-migratory property of 
      I3MO may partly depend on impairment of glycolysis via a compromised STAT3/HK2 
      signaling axis.
CI  - Copyright (c) 2016 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Heiss, Elke H
AU  - Heiss EH
AD  - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, 
      Austria. Electronic address: elke.heiss@univie.ac.at.
FAU - Schachner, Daniel
AU  - Schachner D
AD  - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, 
      Austria.
FAU - Donati, Maddalena
AU  - Donati M
AD  - Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 
      Via Marzolo, 5, 35131 Padova, Italy.
FAU - Grojer, Christoph S
AU  - Grojer CS
AD  - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, 
      Austria.
FAU - Dirsch, Verena M
AU  - Dirsch VM
AD  - Department of Pharmacognosy, University of Vienna, Althanstrasse 14, 1090 Vienna, 
      Austria.
LA  - eng
GR  - P 23317/FWF_/Austrian Science Fund FWF/Austria
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160514
PL  - United States
TA  - Vascul Pharmacol
JT  - Vascular pharmacology
JID - 101130615
RN  - 0 (Indoles)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (Nfe2l2 protein, rat)
RN  - 0 (Oximes)
RN  - 0 (Platelet-Derived Growth Factor)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (Stat3 protein, rat)
RN  - 0 (indirubin-3'-monoxime)
RN  - EC 2.7.1.1 (Hexokinase)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Animals
MH  - CHO Cells
MH  - Cell Movement/*drug effects
MH  - Cricetulus
MH  - Dose-Response Relationship, Drug
MH  - Glycolysis/*drug effects
MH  - Hexokinase/genetics/metabolism
MH  - Indoles/*pharmacology
MH  - Muscle, Smooth, Vascular/*drug effects/metabolism
MH  - Myocytes, Smooth Muscle/*drug effects/metabolism
MH  - NF-E2-Related Factor 2/genetics/metabolism
MH  - Oximes/*pharmacology
MH  - Oxygen/*metabolism
MH  - Platelet-Derived Growth Factor/pharmacology
MH  - RNA Interference
MH  - Rats
MH  - STAT3 Transcription Factor/genetics/metabolism
MH  - Signal Transduction/drug effects
MH  - Time Factors
MH  - Transfection
PMC - PMC4939873
MID - EMS68940
OID - NLM: EMS68940
OTO - NOTNLM
OT  - Aerobic glycolysis
OT  - Hexokinase
OT  - Indirubin-3' monoxime
OT  - Migration
OT  - VSMC
EDAT- 2016/05/18 06:00
MHDA- 2017/06/06 06:00
PMCR- 2016/08/01
CRDT- 2016/05/18 06:00
PHST- 2015/12/15 00:00 [received]
PHST- 2016/04/11 00:00 [revised]
PHST- 2016/05/07 00:00 [accepted]
PHST- 2016/05/18 06:00 [entrez]
PHST- 2016/05/18 06:00 [pubmed]
PHST- 2017/06/06 06:00 [medline]
PHST- 2016/08/01 00:00 [pmc-release]
AID - S1537-1891(15)30107-5 [pii]
AID - 10.1016/j.vph.2016.05.002 [doi]
PST - ppublish
SO  - Vascul Pharmacol. 2016 Aug;83:47-56. doi: 10.1016/j.vph.2016.05.002. Epub 2016 
      May 14.