Estrogen Activates AMP-Activated Protein Kinase in Human Endothelial Cells via ERβ/Ca(2+)/Calmodulin-Dependent Protein Kinase Kinase β Pathway

Songbai Yang, Jing Wang
Cell Biochemistry and Biophysics 2015, 72 (3): 701-7
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 β (CaMKKβ) 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-β (ERβ) activation. Inhibition of CaMKK with STO-609, a specific inhibitor of CaMKKα and CaMKKβ, attenuated E2-induced AMPK activation, suggesting that CaMKKβ 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 CaMKKβ 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 ERβ/Ca(2+)/CaMKKβ-dependent pathway in endothelial cells.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"