PMID- 31116583
OWN - NLM
STAT- MEDLINE
DCOM- 20200323
LR  - 20200930
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Linking)
VI  - 317
IP  - 2
DP  - 2019 Aug 1
TI  - Zinc deficiency promotes endothelin secretion and endothelial cell migration 
      through nuclear hypoxia-inducible factor-1 translocation.
PG  - C270-C276
LID - 10.1152/ajpcell.00460.2018 [doi]
AB  - Zinc is involved in the expression and function of various transcription factors, 
      including the hypoxia-inducible factor-1 (HIF-1). HIF-1 and its target gene 
      endothelin-1 (ET-1) are activated by intermittent hypoxia (IH), one of the main 
      consequences of obstructive sleep apnea (OSA), and both play a key role in the 
      cardiovascular consequences of IH. Because OSA and IH are associated with zinc 
      deficiency, we investigated the effect of zinc deficiency caused by chelation on 
      the HIF-1/ET-1 pathway and its functional consequences in endothelial cells. 
      Primary human microvascular endothelial cells (HMVEC) were incubated with 
      submicromolar doses of the zinc-specific membrane-permeable chelator 
      N,N,N',N'-tetrakis(2-pyridylmethyl)-ethylene diamine (TPEN, 0.5 microM) or ET-1 (0.01 
      microM) with or without bosentan, a dual ET-1-receptor antagonist. HIF-1alpha expression 
      was silenced by transfection with specific siRNA. Nuclear HIF-1 content was 
      assessed by immunofluorescence microscopy and Western blot. Migratory capacity of 
      HMVEC was evaluated with a wound-healing scratch assay. Zinc chelation by TPEN 
      exposure induced the translocation of the cytosolic HIF-1alpha subunit of HIF-1 to 
      the nucleus as well as an HIF-1-mediated ET-1 secretion by HMVEC. Incubation with 
      either TPEN or ET-1 increased endothelial wound-healing capacity. Both HIF-1alpha 
      silencing or bosentan abolished this effect. Altogether, these results suggest 
      that zinc deficiency upregulates ET-1 signaling through HIF-1 activation and 
      stimulates endothelial cell migration, suggesting an important role of zinc in 
      the vascular consequences of IH and OSA mediated by HIF-1-ET- signaling.
FAU - Morand, Jessica
AU  - Morand J
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
FAU - Briancon-Marjollet, Anne
AU  - Briancon-Marjollet A
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
FAU - Lemarie, Emeline
AU  - Lemarie E
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
FAU - Gonthier, Brigitte
AU  - Gonthier B
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
FAU - Arnaud, Josiane
AU  - Arnaud J
AD  - CHUGA, Biochimie Hormonale et nutritionnelle, Grenoble, France.
AD  - Universite Grenoble Alpes, INSERM, Grenoble, France.
FAU - Korichneva, Irina
AU  - Korichneva I
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
AD  - Faculty of Pharmacology and Medicine, University of Picardie Jules Verne, Amiens, 
      France.
FAU - Godin-Ribuot, Diane
AU  - Godin-Ribuot D
AUID- ORCID: 0000-0001-7589-932X
AD  - Universite Grenoble Alpes, INSERM, CHU Grenoble Alpes, Laboratoire HP2, Grenoble, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190522
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Chelating Agents)
RN  - 0 (Endothelin Receptor Antagonists)
RN  - 0 (Endothelin-1)
RN  - 0 (Ethylenediamines)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - J41CSQ7QDS (Zinc)
RN  - Q326023R30 (Bosentan)
RN  - R9PTU1U29I (N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine)
SB  - IM
MH  - Active Transport, Cell Nucleus
MH  - Bosentan/pharmacology
MH  - Cell Movement/*drug effects
MH  - Cells, Cultured
MH  - Chelating Agents/*pharmacology
MH  - Endothelial Cells/*drug effects/metabolism
MH  - Endothelin Receptor Antagonists/pharmacology
MH  - Endothelin-1/genetics/*metabolism
MH  - Ethylenediamines/*pharmacology
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism
MH  - Secretory Pathway
MH  - Signal Transduction
MH  - Zinc/*deficiency
OTO - NOTNLM
OT  - HIF-1alpha
OT  - TPEN
OT  - endothelial cell migration
OT  - endothelin
OT  - zinc
EDAT- 2019/05/23 06:00
MHDA- 2020/03/24 06:00
CRDT- 2019/05/23 06:00
PHST- 2019/05/23 06:00 [pubmed]
PHST- 2020/03/24 06:00 [medline]
PHST- 2019/05/23 06:00 [entrez]
AID - 10.1152/ajpcell.00460.2018 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C270-C276. doi: 
      10.1152/ajpcell.00460.2018. Epub 2019 May 22.