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NOS3 — PRKAA1
Pathways - manually collected, often from reviews:
Text-mined interactions from Literome
Fryer et al., Diabetes 2000
:
A previous study has shown that
AMPK phosphorylates and
activates endothelial nitric oxide synthase (NOS)
Morrow et al., J Biol Chem 2003
:
Expression of dominant negative
AMPK attenuated AICAR stimulated AMPK activity,
eNOS Ser-1177 phosphorylation and NO production and was without effect on AICAR stimulated protein kinase B Ser-473 phosphorylation or NO production stimulated by insulin or A23187 ... These data suggest that AICAR stimulated NO production is mediated by
AMPK as a
consequence of increased Ser-1177 phosphorylation of
eNOS
Chen et al., J Biol Chem 2003
:
Moreover,
AMPK-K45R inhibited phosphorylation of
eNOS at Ser1179 in response to adiponectin but not in response to insulin
Fleming et al., Thromb Haemost 2003
:
AMP activated protein kinase (AMPK) regulates the insulin induced activation of the
nitric oxide synthase in human platelets
Giri et al., J Neurosci 2004
(Inflammation) :
A pharmacological activator of
AMPK , 5-amino-4-imidazole carboxamide riboside ( AICAR )
inhibited lipopolysaccharide (LPS) induced expression of proinflammatory cytokines ( tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 ) and inducible
nitric oxide synthase in primary rat astrocytes, microglia, and peritoneal macrophages
Drew et al., Proc Natl Acad Sci U S A 2004
:
Ser-1179 phosphorylation increased transiently but returned to basal level after 2.5 min. Data demonstrating activation of AMP activated protein kinase (AMPK) during HDL and ApoAI incubation suggests that
AMPK may
play a role in activation of
eNOS ... Collectively, the results indicate that HDL and ApoAI increase
eNOS activity by multisite phosphorylation changes,
involving AMPK activation after protein association between ApoAI and eNOS
McCarty et al., Med Hypotheses 2004
:
Metformin 's antidiabetic efficacy is now known to reflect activation of AMP activated kinase (AMPK) ;
AMPK can
stimulate eNOS , which is expressed in hepatocytes
Thors et al., FEBS Lett 2004
:
Activation of
AMPK using AICAR or CCCP also
resulted in
eNOS phosphorylation
Mount et al., American journal of physiology. Renal physiology 2005
(Acute Disease...) :
Activation of
AMPK in bovine aortic endothelial cells by the ATP depleting agent antimycin A and the antidiabetic drug phenformin also did not
increase phosphorylation of
eNOS-Ser ( 1177 ), confirming that AMPK activation and phosphorylation of eNOS are dissociated in some situations ... Immunoprecipitation studies demonstrated that the dissociation between AMPK activation and phosphorylation of
eNOS-Ser ( 1177 ) was not
due to changes in the physical associations between
AMPK , eNOS, or heat shock protein 90
Schulz et al., Circulation 2005
:
Taken together, these data indicate that
AMPK activity is
essential for estradiol induced
eNOS activation via the promotion of eNOS interaction with HSP90
Davis et al., Diabetes 2006
:
Furthermore, administration of metformin as well as 5-aminoimidazole-4-carboxamide ribonucleoside, an AMPK agonist, significantly increased eNOS Ser1179 phosphorylation, NO bioactivity, and coimmunoprecipitation of eNOS with hsp90 in wild-type C57BL6 mice but not in AMPK-alpha1 knockout mice, suggesting that
AMPK is
required for metformin enhanced
eNOS activation in vivo
Stahmann et al., Mol Cell Biol 2006
(Calcium Signaling) :
Inhibition or downregulation of CaMKKbeta or AMPK abolished phosphorylation of ACC in response to thrombin but had no effect on eNOS phosphorylation, indicating that thrombin stimulated phosphorylation of
eNOS is not
mediated by
AMPK
Levine et al., J Biol Chem 2007
(Calcium Signaling) :
AMP activated protein kinase (AMPK) also
activates eNOS in endothelial cells ; however, the molecular mechanisms linking agonist mediated AMPK regulation with eNOS activation remain incompletely understood ... We studied the
role of
AMPK in VEGF- and S1P mediated
eNOS activation and found that both agonists led to a striking increase in AMPK phosphorylation in pathways involving the calcium/calmodulin dependent protein kinase kinase beta ... Taken together, these results suggest that VEGF and S1P differentially regulate AMPK and establish a central
role for an agonist modulated
AMPK -- > Rac1 -- > Akt axis in the control of
eNOS in endothelial cells
Ropelle et al., Endocrinology 2007
(Anorexia...) :
In parallel, the pharmacological activation of hypothalamic
AMPK in TB animals markedly
reduced the hypothalamic production of inducible
nitric oxide synthase , IL-1beta, and TNF-alpha and modulated the expression of proopiomelanocortin, a hypothalamic neuropeptide that is involved in the control of energy homeostasis
Suzuki et al., Am J Hypertens 2008
(Diabetes Mellitus, Experimental...) :
Activation of
AMPK by cilostazol was through signaling pathway independent of cyclic AMP and
caused phosphorylation of
endothelial nitric oxide synthase (eNOS) , leading to increased production of nitric oxide ( NO ), while inhibiting cytokine induced nuclear factor-kappaB (NF-kappaB) activation, leading to suppression of VCAM-1 gene expression
Li et al., Arterioscler Thromb Vasc Biol 2008
:
The
activation of
eNOS by
AMPK during EPC differentiation provides a novel mechanism for the pleiotropic effects of statins in benefiting the cardiovascular system
Thors et al., Biochim Biophys Acta 2008
:
Conflicting results have been reported concerning the
role of
AMP activated protein kinase (AMPK) in mediating thrombin stimulation of
endothelial NO-synthase (eNOS) ... We also studied the
effects of
AMPK activation on the downstream target
eNOS ... Inhibition of
AMPK by Compound C or AMPK downregulation using siRNA partially
inhibited the phosphorylation of
eNOS in medium 199 but not in 1640, underscoring a clear difference in the pathways mediating thrombin stimulated eNOS phosphorylation in different culture media
Kanazawa et al., Biochem Biophys Res Commun 2008
:
Moreover, metformin significantly activated
AMPK in dose- and time dependent manners, and
induced endothelial nitric oxide synthase (eNOS) and bone morphogenetic protein-2 (BMP-2) expressions
Youn et al., Circ Res 2009
:
These data no doubt provide new insights into the long mystified signaling gap between VEGF receptors and PI3K/AKT or
AMPK dependent
eNOS activation
Martinelli et al., Mol Biol Cell 2009
:
In particular, phosphorylation of
eNOS on S1177 in response to ICAM-1 activation was
regulated by src family protein kinase, rho GTPase, Ca ( 2+ ), CaMKK, and
AMPK , but not Akt/PI3K
Vázquez-Chantada et al., Hepatology 2009
:
Because AMPK is activated by the tumor suppressor kinase LKB1, and
AMPK activates endothelial
nitric oxide ( NO ) synthase ( eNOS ), and NO synthesis is of great importance for hepatocyte proliferation, we hypothesized that in hepatocytes HGF may induce the phosphorylation of LKB1, AMPK, and eNOS through a process regulated by SAMe, and that this cascade might be crucial for hepatocyte growth
Stahmann et al., J Biol Chem 2010
:
We demonstrate that
AMPK does not
mediate eNOS phosphorylation at serine residue 1177 or 633, NO- dependent cGMP generation, or Akt phosphorylation in response to VEGF
Bradley et al., Arterioscler Thromb Vasc Biol 2010
:
Activation of
AMPK by AICAR
activates endothelial
nitric oxide synthase in arteriolar endothelium by increasing its Ser1177 phosphorylation, which leads to vasodilation of resistance arteries and recruitment of microvascular perfusion in muscle
Kim et al., Toxicol Lett 2010
:
In addition, CKS induced
eNOS phosphorylation was
inhibited by the overexpression of a dominant negative mutant form of
AMPK ( DN-AMPK )
Sakakibara et al., Biosci Biotechnol Biochem 2010
:
The inhibitors of cAMP dependent protein kinase (PKA) and
AMP activated protein kinase (AMPK) blocked acetate induced
eNOS phosphorylation in the early and the late phase respectively
Rossoni et al., Clin Sci (Lond) 2011
:
The
effect of
AMPK inhibition ( compound C, 10 µM ) on
eNOS phosphorylation and contractile responses were also studied
Cacicedo et al., Am J Physiol Heart Circ Physiol 2011
:
The results also suggest that
AMPK likely is the principal
activator of
eNOS in this setting and that its own activation may be mediated by both SIRT1-LKB1 and CaMKKß
Centeno-Baez et al., Am J Physiol Endocrinol Metab 2011
:
Resveratrol inhibition of inducible
nitric oxide synthase in skeletal muscle
involves AMPK but not SIRT1
Chung et al., Exp Mol Med 2012
:
A phospholipase C (PLC) inhibitor blocked the increases in intracellular Ca ( 2+ ) levels,
AMPK dependent
eNOS phosphorylation, and NO production, but not Akt activation, in syringaresinol- treated endothelial cells
Wu et al., PloS one 2012
:
The aim of the present study was to test the hypothesis that the cardiovascular-protective effects of eicosapentaenoic acid ( EPA ) may be due, in part, to its ability to stimulate the
AMP activated protein kinase (AMPK) induced
endothelial nitric oxide synthase (eNOS) activation ... The
role of
AMPK in EPA induced
eNOS phosphorylation was investigated in bovine aortic endothelial cells ( BAEC ), in mice deficient of either AMPKa1 or AMPKa2, in eNOS knockout ( KO ) mice, or in Apo-E/AMPKa1 dual KO mice