2008
DOI: 10.1016/j.bbamcr.2008.07.003
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Mechanism of thrombin mediated eNOS phosphorylation in endothelial cells is dependent on ATP levels after stimulation

Abstract: Conflicting results have been reported concerning the role of AMP-activated protein kinase (AMPK) in mediating thrombin stimulation of endothelial NO-synthase (eNOS). We examined the involvement of two upstream kinases in AMPK activation in cultured human umbilical endothelial cells, LKB1 stimulated by a rise in intracellular AMP/ATP ratio, and Ca(+2)/CaM kinase kinase (CaMKK) responding to elevation of intracellular Ca(+2). We also studied the effects of AMPK activation on the downstream target eNOS. In cultu… Show more

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Cited by 21 publications
(21 citation statements)
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“…Mitochondrial membrane depolarization is expected to lower cellular ATP levels and thereby increase the AMP: ATP ratio [38,52]. The mechanism proposed in this study is similar to the mechanism of histamine and thrombin-induced eNOS activation [13,14]. Meanwhile, this acute elevation of AMP: ATP ratio recovered within 24 h which was also in accordance with the aforementioned transient activation of AMPK in in-vitro conditions.…”
Section: Discussionsupporting
confidence: 88%
See 1 more Smart Citation
“…Mitochondrial membrane depolarization is expected to lower cellular ATP levels and thereby increase the AMP: ATP ratio [38,52]. The mechanism proposed in this study is similar to the mechanism of histamine and thrombin-induced eNOS activation [13,14]. Meanwhile, this acute elevation of AMP: ATP ratio recovered within 24 h which was also in accordance with the aforementioned transient activation of AMPK in in-vitro conditions.…”
Section: Discussionsupporting
confidence: 88%
“…In response to several stimuli, including metformin [11], adiponectin [12], thrombin and histamine [13,14], and vascular endothelial growth factor [15], AMPK is activated and in turn acts as a direct activator of eNOS [16] by phosphorylating its serine 1177 site. There are also evidences that AMPK lies upstream of the PI3K/Akt pathway, which also leads to eNOS activation and NO production [15,17,18].…”
Section: Introductionmentioning
confidence: 99%
“…These data indicate that AMPK activation and eNOS phosphorylation may be dissociated when AMPK is activated by metabolic stress. Moreover, eNOS did not become an AMPK substrate when cells were stimulated with VEGF in the presence of 2-deoxyglucose as suggested previously (65). The combined addition of LKB1-siRNA and STO-609 completely prevented the phosphorylation of AMPK induced by VEGF plus 2-deoxyglucose but had FIGURE 3.…”
Section: Vegf-induced Ampk Activation Is Not Mediated By the No/guanylylmentioning
confidence: 71%
“…The situation may differ depending on the cell type and the specific circumstances of stimulation. A recent study, for example, suggests that eNOS may become AMPKresponsive under conditions of ATP depletion (65); these authors show that thrombin phosphorylates eNOS via the CaMKK␤/AMPK pathway only when cellular ATP is lowered, for instance when cells are preincubated with 2-deoxyglucose. Another study reports that serine 1177 phosphorylation of eNOS by AMPK occurs only in hypoxic but not in normoxic conditions (10).…”
Section: Figure 5 Vegf-induced Acc Phosphorylation But Not Enos Phosmentioning
confidence: 99%
“…9,10 In the second series of studies, to examine the involvement of protein kinase A (PKA) and AMP-activated protein kinase (AMPK), we studied the cilostazolinduced response after incubation with the PKA inhibitor, Rp-8-BrcAMPS (100 lM), 19 and the AMPK inhibitor, compound C (10 lM). 20 …”
Section: Mechanistic Studies Of Cilostazol-induced Dilationmentioning
confidence: 99%