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Thrombin and histamine stimulate endothelial nitric‐oxide synthase phosphorylation at Ser1177 via an AMPK mediated pathway independent of PI3K‐Akt
Author(s) -
Thors Brynhildur,
Halldórsson Haraldur,
Thorgeirsson Gudmundur
Publication year - 2004
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.07.078
Subject(s) - ampk , enos , phosphorylation , amp activated protein kinase , protein kinase a , protein kinase b , chemistry , medicine , pi3k/akt/mtor pathway , endocrinology , microbiology and biotechnology , signal transduction , nitric oxide synthase , biology , biochemistry , nitric oxide
Histamine and thrombin cause phosphorylation and activation of endothelial NO‐synthase (eNOS) on Ser1177. We tested the role of various protein kinases in mediating this effect in human umbilical vein endothelial cells. Inhibition of the Ca 2+ /calmodulin‐dependent protein kinase II or phosphoinositide 3‐kinase (PI3K) had no effect. H89, an inhibitor of both protein kinase A (PKA) and 5 ′ ‐AMP‐activated protein kinase (AMPK), strongly inhibited phosphorylation and activity of eNOS. Conversely, the PKA inhibitor Rp‐adenosine 3 ′ 5 ′ ‐cyclic monophosphate (cAMPS) had no effect and eNOS was not phosphorylated by treatments that affect cAMP levels. Thrombin and histamine caused phosphorylation of AMPK on Thr172 as well as on its downstream target acetyl‐CoA carboxylase. Activation of AMPK using AICAR or CCCP also resulted in eNOS phosphorylation. We conclude that histamine and thrombin cause eNOS phosphorylation in an AMPK mediated manner, independent of P13K‐Akt.