PMID- 17586470
OWN - NLM
STAT- MEDLINE
DCOM- 20070905
LR  - 20181113
IS  - 0006-291X (Print)
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 360
IP  - 1
DP  - 2007 Aug 17
TI  - Metallothionein rescues hypoxia-inducible factor-1 transcriptional activity in 
      cardiomyocytes under diabetic conditions.
PG  - 286-9
AB  - Metallothionein (MT) is effective in the prevention of diabetic cardiomyopathy, 
      and hypoxia-inducible factor-1 (HIF-1) is known to control vascular endothelial 
      growth factor (VEGF) gene expression and regulate angiogenesis in diabetic 
      hearts. We examined whether or not MT affects HIF-1 activity in the heart of 
      diabetic mice and in the cardiac cells cultured in high glucose (HG) media. 
      Diabetes was induced by streptozotocin in a cardiac-specific MT overexpressing 
      transgenic mouse model. The primary cultures of neonatal cardiomyocytes and the 
      embryonic rat cardiac H9c2 cell line were cultured in HG media. HIF-1 and VEGF 
      were determined by immunofluorescent staining and enzyme-linked immunosorbent 
      assay, respectively. The H9c2 cells were transfected with a hypoxia-responsive 
      element-dependent reporter plasmid and the HIF-1 transcriptional activity was 
      measured by luciferase reporter assay. MT overexpression increased HIF-1alpha in 
      diabetic hearts. HG suppressed CoCl(2)-induced VEGF expression in primary 
      cultures of neonatal cardiomyocytes and MT overexpression suppressed the 
      inhibition. The addition of MT into the cultures of H9c2 cells relieved the HG 
      suppression of hypoxia-induced luciferase activity. This study indicates that MT 
      can rescue HIF-1 transcriptional activity in cardiomyocytes under diabetic 
      conditions.
FAU - Feng, Wenke
AU  - Feng W
AD  - Department of Medicine, University of Louisville School of Medicine, 511 S Floyd 
      Street, MDR532, Louisville, KY 40202, USA.
FAU - Wang, Yuehui
AU  - Wang Y
FAU - Cai, Lu
AU  - Cai L
FAU - Kang, Y James
AU  - Kang YJ
LA  - eng
GR  - R01 HL059225/HL/NHLBI NIH HHS/United States
GR  - R01 HL063760/HL/NHLBI NIH HHS/United States
GR  - HL59225/HL/NHLBI NIH HHS/United States
GR  - HL63760/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20070619
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Hif1a protein, mouse)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 9038-94-2 (Metallothionein)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Diabetes Mellitus/*metabolism
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/*metabolism
MH  - Metallothionein/genetics/*metabolism
MH  - Mice
MH  - Mice, Transgenic
MH  - Myocytes, Cardiac/*metabolism
MH  - *Transcriptional Activation
PMC - PMC3458699
MID - NIHMS27488
EDAT- 2007/06/26 09:00
MHDA- 2007/09/06 09:00
PMCR- 2012/09/26
CRDT- 2007/06/26 09:00
PHST- 2007/06/04 00:00 [received]
PHST- 2007/06/12 00:00 [accepted]
PHST- 2007/06/26 09:00 [pubmed]
PHST- 2007/09/06 09:00 [medline]
PHST- 2007/06/26 09:00 [entrez]
PHST- 2012/09/26 00:00 [pmc-release]
AID - S0006-291X(07)01299-5 [pii]
AID - 10.1016/j.bbrc.2007.06.057 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2007 Aug 17;360(1):286-9. doi: 
      10.1016/j.bbrc.2007.06.057. Epub 2007 Jun 19.