PMID- 23153326
OWN - NLM
STAT- MEDLINE
DCOM- 20130625
LR  - 20131121
IS  - 1029-2470 (Electronic)
IS  - 1029-2470 (Linking)
VI  - 47
IP  - 2
DP  - 2013 Feb
TI  - Hydrogen peroxide induces overexpression of angiotensin-converting enzyme in 
      human umbilical vein endothelial cells.
PG  - 116-22
LID - 10.3109/10715762.2012.749987 [doi]
AB  - Oxidative stress has been linked to endothelial dysfunction in atherosclerosis 
      and hypertension. The present study was designed to investigate the effect of 
      hydrogen peroxide (H2O2) on angiotensin-converting enzyme (ACE), a key regulator 
      of the renin-angiotensin system, and the mechanisms underlying ACE regulation in 
      human umbilical vein endothelial cells (HUVECs). We used Tetrazolium bromide 
      (MTT) assay for cell viability, terminal deoxynucleotidyl transferase-mediated 
      dUTP nick end labeling (TUNEL) assay for cell apoptosis, enzyme-linked 
      immunosorbent assay (ELISA) for cAMP measurement, real-time PCR for mRNA 
      detection, and Western blot for protein analysis in the study. Our results 
      demonstrated that H2O2 (50-1000 muM) decreased HUVECs viability by inducing 
      apoptosis. Notably, H2O2 upregulated ACE expression in a concentration-dependent 
      manner. H2O2 100 muM significantly enhanced cyclic adenosine monophosphate (cAMP) 
      expression by 1.48-fold (P<0.05). Additionally, forskolin 10 muM, a cAMP agonist, 
      was also found to enhance ACE expression by 1.78-fold (P<0.05); in contrast, H-89 
      10 muM, a protein kinase A (PKA) inhibitor, abolished H2O2-induced ACE expression 
      and prevented the enhancing effect of forskolin-induced ACE expression. Similar 
      effects on ACE mRNA were also observed. cAMP-response element-specific decoy 
      oligodeoxynucleotides (CRE-dODN) containing binding sites for cAMP-response 
      element-binding protein (CREB) inhibited ACE expression at both the mRNA and 
      protein levels. Negative control CRE-dODN had no effect on ACE expression. We 
      conclude that H2O2 upregulates the expression of ACE through the activation of 
      cAMP/PKA/CREB signal pathway in HUVECs, indicating a role of oxidative stress in 
      the pathophysiology of hypertension.
FAU - Mu, Xiaoqin
AU  - Mu X
AD  - Department of Pharmacology, Harbin Medical University, Harbin, PR China.
FAU - He, Kaiwen
AU  - He K
FAU - Sun, Hui
AU  - Sun H
FAU - Zhou, Xin
AU  - Zhou X
FAU - Chang, Lingling
AU  - Chang L
FAU - Li, Xin
AU  - Li X
FAU - Chu, Wenfeng
AU  - Chu W
FAU - Qiao, Guofen
AU  - Qiao G
FAU - Lu, Yanjie
AU  - Lu Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121210
PL  - England
TA  - Free Radic Res
JT  - Free radical research
JID - 9423872
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (RNA, Messenger)
RN  - 1F7A44V6OU (Colforsin)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases)
RN  - EC 3.4.15.1 (Peptidyl-Dipeptidase A)
SB  - IM
MH  - Apoptosis
MH  - CREB-Binding Protein/metabolism
MH  - Cell Line
MH  - Cell Survival
MH  - Colforsin/pharmacology
MH  - Cyclic AMP/antagonists & inhibitors/metabolism
MH  - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors/metabolism
MH  - Endothelial Cells/metabolism
MH  - Human Umbilical Vein Endothelial Cells/*metabolism
MH  - Humans
MH  - Hydrogen Peroxide/*pharmacology
MH  - Hypertension
MH  - In Situ Nick-End Labeling
MH  - Oligodeoxyribonucleotides/metabolism
MH  - *Oxidative Stress
MH  - Peptidyl-Dipeptidase A/biosynthesis/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Signal Transduction
MH  - Transcriptional Activation
EDAT- 2012/11/17 06:00
MHDA- 2013/06/26 06:00
CRDT- 2012/11/17 06:00
PHST- 2012/11/17 06:00 [entrez]
PHST- 2012/11/17 06:00 [pubmed]
PHST- 2013/06/26 06:00 [medline]
AID - 10.3109/10715762.2012.749987 [doi]
PST - ppublish
SO  - Free Radic Res. 2013 Feb;47(2):116-22. doi: 10.3109/10715762.2012.749987. Epub 
      2012 Dec 10.