PMID- 30352976
OWN - NLM
STAT- MEDLINE
DCOM- 20190115
LR  - 20190115
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 11
DP  - 2018 Oct 24
TI  - Copper(II) Bis(diethyldithiocarbamate) Induces the Expression of Syndecan-4, a 
      Transmembrane Heparan Sulfate Proteoglycan, via p38 MAPK Activation in Vascular 
      Endothelial Cells.
LID - 10.3390/ijms19113302 [doi]
LID - 3302
AB  - Proteoglycans synthesized by vascular endothelial cells are important for 
      regulating cell function and the blood coagulation-fibrinolytic system. Since we 
      recently reported that copper(II) bis(diethyldithiocarbamate) (Cu(edtc)(2)) 
      modulates the expression of some molecules involving the antioxidant and blood 
      coagulation systems, we hypothesized that Cu(edtc)(2) may regulate the expression 
      of proteoglycans and examined this hypothesis using a bovine aortic endothelial 
      cell culture system. The experiments showed that Cu(edtc)(2) induced the expression 
      of syndecan-4, a transmembrane heparan sulfate proteoglycan, in a dose- and 
      time-dependent manner. This induction required the whole structure of 
      Cu(edtc)(2)-the specific combination of intramolecular copper and a 
      diethyldithiocarbamate structure-as the ligand. Additionally, the syndecan-4 
      induction by Cu(edtc)(2) depended on the activation of p38 mitogen-activated 
      protein kinase (MAPK) but not the Smad2/3, NF-E2-related factor2 (Nrf2), or 
      epidermal growth factor receptor (EGFR) pathways. p38 MAPK may be a key molecule 
      for inducing the expression of syndecan-4 in vascular endothelial cells.
FAU - Hara, Takato
AU  - Hara T
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science, 2641 Yamazaki, Noda 278-8510, Japan. 
      takato.hara@phar.toho-u.ac.jp.
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi 274-8510, Japan. 
      takato.hara@phar.toho-u.ac.jp.
FAU - Tatsuishi, Hiroko
AU  - Tatsuishi H
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science, 2641 Yamazaki, Noda 278-8510, Japan. 
      j3a12066@ed.tus.ac.jp.
FAU - Banno, Tomomi
AU  - Banno T
AD  - Graduate School of Science, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 
      464-8602, Japan. banno.tomomi@a.mbox.nagoya-u.ac.jp.
FAU - Fujie, Tomoya
AU  - Fujie T
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi 274-8510, Japan. t-fujie@phar.toho-u.ac.jp.
FAU - Yamamoto, Chika
AU  - Yamamoto C
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Toho 
      University, 2-2-1 Miyama, Funabashi 274-8510, Japan. yamamoto@phar.toho-u.ac.jp.
FAU - Naka, Hiroshi
AU  - Naka H
AUID- ORCID: 0000-0002-1198-6835
AD  - Research Center for Materials Science, Nagoya University, Furo-cho, Chikusa-ku, 
      Nagoya 464-8602, Japan. h_naka@nagoya-u.jp.
FAU - Kaji, Toshiyuki
AU  - Kaji T
AD  - Department of Environmental Health, Faculty of Pharmaceutical Sciences, Tokyo 
      University of Science, 2641 Yamazaki, Noda 278-8510, Japan. t-kaji@rs.tus.ac.jp.
LA  - eng
GR  - Fusion Emergent Research, 2018/Integrated Research Consortium on Chemical 
      Sciences/
PT  - Journal Article
DEP - 20181024
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Organometallic Compounds)
RN  - 0 (Syndecan-4)
RN  - 789U1901C5 (Copper)
RN  - 99Z2744345 (Ditiocarb)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Animals
MH  - Cattle
MH  - Cells, Cultured
MH  - Copper/chemistry
MH  - Ditiocarb/analogs & derivatives
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Endothelium, Vascular/metabolism
MH  - Organometallic Compounds/*pharmacology
MH  - Syndecan-4/genetics/*metabolism
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
PMC - PMC6274924
OTO - NOTNLM
OT  - bioorganometallics
OT  - metal coordination complexes
OT  - organocopper compound
OT  - proteoglycan
OT  - syndecan-4
OT  - vascular endothelial cell
COIS- The authors declare no conflict of interest.
EDAT- 2018/10/26 06:00
MHDA- 2019/01/16 06:00
PMCR- 2018/11/01
CRDT- 2018/10/25 06:00
PHST- 2018/09/20 00:00 [received]
PHST- 2018/10/18 00:00 [revised]
PHST- 2018/10/21 00:00 [accepted]
PHST- 2018/10/25 06:00 [entrez]
PHST- 2018/10/26 06:00 [pubmed]
PHST- 2019/01/16 06:00 [medline]
PHST- 2018/11/01 00:00 [pmc-release]
AID - ijms19113302 [pii]
AID - ijms-19-03302 [pii]
AID - 10.3390/ijms19113302 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Oct 24;19(11):3302. doi: 10.3390/ijms19113302.