PMID- 25825815
OWN - NLM
STAT- MEDLINE
DCOM- 20150819
LR  - 20150518
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 156
IP  - 6
DP  - 2015 Jun
TI  - MiR-22/Sp-1 Links Estrogens With the Up-Regulation of Cystathionine gamma-Lyase in 
      Myocardium, Which Contributes to Estrogenic Cardioprotection Against Oxidative 
      Stress.
PG  - 2124-37
LID - 10.1210/en.2014-1362 [doi]
AB  - Hydrogen sulfide, generated in the myocardium predominantly via 
      cystathionine-gamma-lyase (CSE), is cardioprotective. Our previous study has shown 
      that estrogens enhance CSE expression in myocardium of female rats. The present 
      study aims to explore the mechanisms by which estrogens regulate CSE expression, 
      in particular to clarify the role of estrogen receptor subtypes and the 
      transcriptional factor responsible for the estrogenic effects. We found that 
      either the CSE inhibitor or the CSE small interfering RNA attenuated the 
      protective effect of 17beta-estradiol (E2) against H2O2- and 
      hypoxia/reoxygenation-induced injury in primary cultured neonatal cardiomyocytes. 
      E2 stimulates CSE expression via estrogen receptor (ER)-alpha both in cultured 
      cardiomyocytes in vitro and in the myocardium of female mice in vivo. A 
      specificity protein-1 (Sp-1) consensus site was identified in the rat CSE 
      promoter and was found to mediate the E2-induced CSE expression. E2 increases ERalpha 
      and Sp-1 and inhibits microRNA (miR)-22 expression in myocardium of 
      ovariectomized rats. In primary cardiomyocytes, E2 stimulates Sp-1 expression 
      through the ERalpha-mediated down-regulation of miR-22. It was confirmed that both 
      ERalpha and Sp-1 were targeted by miR-22. In the myocardium of ovariectomized rats, 
      the level of miR-22 inversely correlated to CSE, ERalpha, Sp-1, and antioxidant 
      biomarkers and positively correlated to oxidative biomarkers. In summary, this 
      study demonstrates that estrogens stimulate Sp-1 through the ERalpha-mediated 
      down-regulation of miR-22 in cardiomyocytes, leading to the up-regulation of CSE, 
      which in turn results in an increase of antioxidative defense. Interaction of 
      ERalpha, miR-22, and Sp-1 may play a critical role in the control of oxidative stress 
      status in the myocardium of female rats.
FAU - Wang, Long
AU  - Wang L
AD  - Department of Physiology and The Key Laboratory of Molecular Neurobiology of the 
      Ministry of Education (L.W., W.Z., B.-H.C., X.-L.T., X.-H.L., X.-Y.Z., X.N.), 
      Second Military Medical University, and School of Kinesiology (Z.-P.T., J.-Q.L.), 
      Key laboratory of Exercise and Health Science of the Ministry of Education, 
      Shanghai University of Sport, Shanghai 200433, China.
FAU - Tang, Zhi-Ping
AU  - Tang ZP
FAU - Zhao, Wei
AU  - Zhao W
FAU - Cong, Bing-Hai
AU  - Cong BH
FAU - Lu, Jian-Qiang
AU  - Lu JQ
FAU - Tang, Xiao-Lu
AU  - Tang XL
FAU - Li, Xiao-Han
AU  - Li XH
FAU - Zhu, Xiao-Yan
AU  - Zhu XY
FAU - Ni, Xin
AU  - Ni X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150331
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Estrogens)
RN  - 0 (MIRN22 microRNA, rat)
RN  - 0 (MicroRNAs)
RN  - 0 (Mirn22 microRNA, mouse)
RN  - 0 (Sp1 Transcription Factor)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 4.4.1.1 (Cystathionine gamma-Lyase)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Cystathionine gamma-Lyase/genetics/*metabolism
MH  - Estradiol/pharmacology
MH  - Estrogens/*pharmacology
MH  - Female
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - MicroRNAs/*metabolism
MH  - Myocardium/*metabolism
MH  - Oxidative Stress/*drug effects
MH  - RNA Interference
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Sp1 Transcription Factor/*metabolism
EDAT- 2015/04/01 06:00
MHDA- 2015/08/20 06:00
CRDT- 2015/04/01 06:00
PHST- 2015/04/01 06:00 [entrez]
PHST- 2015/04/01 06:00 [pubmed]
PHST- 2015/08/20 06:00 [medline]
AID - 10.1210/en.2014-1362 [doi]
PST - ppublish
SO  - Endocrinology. 2015 Jun;156(6):2124-37. doi: 10.1210/en.2014-1362. Epub 2015 Mar 
      31.