PMID- 25616441
OWN - NLM
STAT- MEDLINE
DCOM- 20170119
LR  - 20171116
IS  - 1559-0283 (Electronic)
IS  - 1085-9195 (Linking)
VI  - 72
IP  - 3
DP  - 2015 Jul
TI  - Estrogen Activates AMP-Activated Protein Kinase in Human Endothelial Cells via 
      ERbeta/Ca(2+)/Calmodulin-Dependent Protein Kinase Kinase beta Pathway.
PG  - 701-7
LID - 10.1007/s12013-015-0521-z [doi]
AB  - Our previous studies suggested that Estrogen inhibits cytokine-induced expression 
      of VCAM-1 and ICAM-1 in cultured human endothelial cells via AMP-activated 
      protein kinase (AMPK) activation. Here, we sought to delineate the mechanisms 
      underlying estrogen activation of AMPK. AMPK can be considered a 'fuel gauge' of 
      cellular energy status in response to metabolic stress. It is controlled by 
      upstream kinases such as Ca(2+)/calmodulin-dependent protein kinase kinase beta 
      (CaMKKbeta) or LKB1. The present study of human endothelial cells demonstrates that 
      AMPK is activated by estradiol (E2) through a Ca(2+)-dependent mechanism 
      involving the estrogen receptor-beta (ERbeta) activation. Inhibition of CaMKK with 
      STO-609, a specific inhibitor of CaMKKalpha and CaMKKbeta, attenuated E2-induced AMPK 
      activation, suggesting that CaMKKbeta was the responsible AMPK kinase. Conversely, 
      down-regulation of LKB1 did not affect E2-induced AMPK activation. E2 stimulation 
      caused phosphorylation of acetyl coenzyme A carboxylase (ACC) and endothelial 
      nitric oxide synthase (eNOS), two main targets of AMPK. Inhibition or 
      down-regulation of CaMKKbeta eliminated phosphorylation of ACC and eNOS in response 
      to E2. Together, our data highlight the role of Ca(2+) as a regulator of AMPK 
      activation in response to E2 stimulation. We demonstrate that E2 activates AMPK 
      via an ERbeta/Ca(2+)/CaMKKbeta-dependent pathway in endothelial cells.
FAU - Yang, Songbai
AU  - Yang S
AD  - Department of Vascular Surgery, China-Japan Union Hospital of Jilin University, 
      Changchun, People's Republic of China.
FAU - Wang, Jing
AU  - Wang J
AD  - School of Life Sciences, Jilin Agricultural University, 2888 Xincheng Street, 
      Changchun, 130118, People's Republic of China. jingchinw@163.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cell Biochem Biophys
JT  - Cell biochemistry and biophysics
JID - 9701934
RN  - 0 (Benzimidazoles)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Estrogens)
RN  - 0 (Naphthalimides)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (STO 609)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type III)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 1)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - EC 6.4.1.2 (Acetyl-CoA Carboxylase)
SB  - IM
MH  - AMP-Activated Protein Kinases/*metabolism
MH  - Acetyl-CoA Carboxylase/metabolism
MH  - Benzimidazoles/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 1/antagonists & 
      inhibitors/*metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Estradiol/*pharmacology
MH  - Estrogen Receptor beta/*metabolism
MH  - Estrogens/*pharmacology
MH  - Humans
MH  - Naphthalimides/pharmacology
MH  - Nitric Oxide Synthase Type III/metabolism
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction
OTO - NOTNLM
OT  - AMP-activated protein kinase (AMPK)
OT  - Acetyl coenzyme A carboxylase (ACC)
OT  - Calmodulin-dependent protein kinase kinase beta (CaMKKbeta)
OT  - Endothelial nitric oxide synthase (eNOS)
OT  - Estradiol (E2)
OT  - Estrogen receptor-beta (ERbeta)
EDAT- 2015/01/27 06:00
MHDA- 2017/01/20 06:00
CRDT- 2015/01/25 06:00
PHST- 2015/01/25 06:00 [entrez]
PHST- 2015/01/27 06:00 [pubmed]
PHST- 2017/01/20 06:00 [medline]
AID - 10.1007/s12013-015-0521-z [pii]
AID - 10.1007/s12013-015-0521-z [doi]
PST - ppublish
SO  - Cell Biochem Biophys. 2015 Jul;72(3):701-7. doi: 10.1007/s12013-015-0521-z.