| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :1.1881176 |
| Here we show that Hsp 90 associates with endothelial nitric oxide synthase ( eNOS ) and is rapidly recruited to the eNOS complex by agonists that stimulate production of nitric oxide , namely vascular endothelial growth factor , histamine and fluid shear stress . 1.1881176^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :1.1816217 |
| Accordingly , we showed that early VEGF stimulation first leads to the Ca ( 2+ ) / calmodulin disruption of the caveolin eNOS complex and promotes the association between eNOS and hsp 90 . eNOS bound hsp 90 can then recruit VEGF activated ( phosphorylated ) Akt to the complex , which in turn can phosphorylate eNOS . 1.1816217^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.72500436 |
| In contrast , n LDL decreased cGMP under basal and A 23187 stimulated conditions and increased O ( 2 ) ( * ) by a mechanism that could be inhibited by L nitroargininemethylester ( L NAME ) and BAPTA / AM . n LDL increased phospho eNOS by 149 % , eNOS by approximately 34 % , and Cav 1 by 28 % , and decreased the association of hsp 90 with eNOS by 49 % . n LDL did not appear to alter eNOS distribution between membrane fractions ( approximately 85 % ) and cytosol ( approximately 15 % ) . 0.72500436^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.70844744 |
| Taken together , these data indicate that the association of hsp 90 with eNOS is important for increasing * NO production and limiting eNOS dependent superoxide anion generation . 0.70844744^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.61807546 |
| Although recent reports indicate that heat shock protein 90 ( hsp 90 ) associates with eNOS to increase ( * ) NO generation , the role of hsp 90 association with eNOS during endothelial cell proliferation remains unknown . 0.61807546^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.93441969 |
| Association of hsp 90 with eNOS was determined in rat aortas and bovine aortic endothelial cells ( BAECs ) . 0.93441969^^^ Angiostatin decreased the association of hsp 90 with eNOS in aortas and BAEC cultures and increased O 2 generation in stimulated BAECs by an Lgamma nitroargininemethylester ( L NAME ) inhibitable mechanism . 0.81389722^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.53482627 |
| Stimulation of endothelial cells incubated with LDL decreased the association of hsp 90 with eNOS . 0.53482627^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.5074758 |
| TRI decreased hsp 90 associated with eNOS by 46 . 7 % and inhibited VEGF stimulated endothelial cell proliferation by 12 to 35 % . 0.5074758^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.81493958 |
| Association of HSP 90 with eNOS and NO release increased in response to ATP in control pulmonary artery endothelial cells , but not in cells from PPHN lambs . 0.81493958^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.55869073 |
| In addition , the molecular chaperone Hsp 90 interacts with eNOS and positively regulates eNOS activity . 0.55869073^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.72552779 |
| Hypoxia further decreased association of HSP 90 with eNOS in lungs of SCD and heterozygote SCD mice , but not in the control lungs . 0.72552779^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.8119033 |
| The present study was designed to determine the involvement of protein interactions between eNOS and HSP 90 in high glucose induced endothelial cell apoptosis . 0.8119033^^^ The results showed that the protein interactions between eNOS and HSP 90 and between eNOS and Akt and the phosphorylation of eNOS were up regulated by high glucose exposure for 2 4 h . 0.65806074^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.71188481 |
| Co immunoprecipitation experiments consistently showed increased association of hsp 90 with eNOS after exposure of cells to S1P as well to BK or calcium ionophore A 23187 . 0.71188481^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.55741688 |
| CONCLUSIONS : These results indicate that chronic EtOH exposure increases endothelial NO production by increasing eNOS protein levels through PI 3 K dependent up regulation of eNOS gene transcription and by increasing interactions between eNOS and hsp 90 . 0.55741688^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.65776171 |
| Finally , incubation of BAECs with clinically relevant concentrations of metformin dramatically attenuated high glucose ( 30 mmol / l ) induced reduction in the association of hsp 90 with eNOS , which resulted in increased NO bioactivity with a reduction in overexpression of adhesion molecules and endothelial apoptosis caused by high glucose exposure . 0.65776171^^^ Furthermore , administration of metformin as well as 5 aminoimidazole 4 carboxamide ribonucleoside , an AMPK agonist , significantly increased eNOS Ser 1179 phosphorylation , NO bioactivity , and coimmunoprecipitation of eNOS with hsp 90 in wild type C57BL6 mice but not in AMPK alpha 1 knockout mice , suggesting that AMPK is required for metformin enhanced eNOS activation in vivo . 0.54160073^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.54052001 |
| Because co immunoprecipitation of eNOS with both Hsp 90 and caveolin similarly decreased in cirrhotic rats , eNOS activity was not modified by this mechanism . 0.54052001^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.51116592 |
| We conclude increased association of hsp 90 with NOS 3 is a major mechanism by which BN / Mcw hearts are more resistant to ischemia than SS / Mcw hearts . . 0.51116592^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Previously , it has been reported that the hsp 90 inhibitor geldanamycin uncouples endothelial NOS activity and increases endothelial NOS dependent O ( 2 ) ( ) production . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Expression of ER beta and ER alpha receptors , endothelial NOS ( eNOS ) , HSP 70 , and HSP 90 increased with ovariectomy . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Tissue levels of connexins 40 , 43 ( major components of gap junction ) , inducible NOS ( iNOS ) , endothelial NOS ( eNOS ) and eNOS regulator proteins such as calmodulin , heat shock protein 90 ( hsp 90 ) and caveolin 1 were also examined using Western blot . 2 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| The molecular chaperone , heat shock protein 90 ( Hsp 90 ) , acts as an intermediate in the signaling cascades leading to activation of endothelial nitric oxide synthase ( eNOS ) . ^^^ In normal animals , immunoprecipitation of eNOS from intact mesentery coimmunoprecipitates Hsp 90 and , additionally , both eNOS and Hsp 90 colocalize to the endothelial lining of mesenteric vessels . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| These benzoquinone ansamycins are potent inhibitors of Hsp 90 function , which has recently been shown to play a role in stimulus dependent eNOS activation . ^^^ As in response to shear , E ( 2 ) induced an Hsp 90 eNOS association , peaking at 30 min and completely inhibited by the conventional estrogen receptor antagonist ICI 182 , 780 . ^^^ These findings suggest that Hsp 90 plays an important role in the rapid , estrogen receptor mediated modulation of eNOS activation by estrogen . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Additional post translational mechanisms regulate the activity of eNOS , including the interaction of eNOS with caveolin 1 , heat shock protein 90 ( Hsp 90 ) , or membrane phospholipids , as well as enzyme translocation and phosphorylation . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Other caveolar proteins appear to contribute to the eNOS membrane complex , including the bradykinin B 2 receptor , the angiotensin AT 1 receptor , the CAT 1 arginine transporter , and Hsp 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Reconstitution of an endothelial nitric oxide synthase ( eNOS ) , hsp 90 , and caveolin 1 complex in vitro . ^^^ Evidence that hsp 90 facilitates calmodulin stimulated displacement of eNOS from caveolin 1 . ^^^ The association of eNOS with caveolin 1 ( Cav ) is believed to maintain eNOS in an inactive state ; however , increased association of eNOS to heat shock protein 90 ( hsp 90 ) is observed following activation . ^^^ In this study , we investigate the relationship between caveolin and hsp 90 as opposing regulatory proteins on eNOS function . ^^^ Immunoprecipitation of Cav 1 from bovine lung microvascular endothelial cells shows that eNOS and hsp 90 are present in the Cav 1 complex . eNOS and hsp 90 from the lysate also interact with exogenous glutathione S transferase linked caveolin 1 ( GST Cav ) , and the addition of calcium activated calmodulin ( CaM ) to the GST Cav complex partially inhibited the association of eNOS and hsp 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Moreover , the HSP 90 content in anti eNOS antibody induced immunoprecipitates from hypoxic PAEC lysates was reduced , and repletion of HSP 90 reversed the decrease of eNOS activity in these immunoprecipitates . ^^^ Incubation of PAEC with a specific inhibitor of HSP 90 ( geldanamycin ) mimicked the hypoxic decrease of eNOS activity . ^^^ These results indicate that the hypoxia induced reduction in eNOS activity in PAEC is due to a decrease in HSP 90 caused by calpain activation . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| The interaction between Hsp 90 and eNOS enhances the activation of the enzyme in cells and in intact blood vessels leading to NO production . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Heat shock protein 90 ( HSP 90 ) , an essential component of several signal transduction systems , participates in the activation of endothelial nitric oxide synthase ( eNOS ) in cells . ^^^ The objective of the current study was to determine if HSP 90 and eNOS were functionally interdependent and colocalized in the cerebral circulation . ^^^ Furthermore , RIA showed significant reduction in cGMP levels in arteries treated with geldanamycin ( 3 microg / mL ; P < 0 . 02 , n = 8 ) , whereas immunogold EM demonstrated areas of colocalization of HSP 90 and eNOS selectively in the cytoplasm of endothelial cells . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In the presence of LDL Chol , atorvastatin also promoted the agonist induced association of eNOS and the chaperone Hsp 90 , resulting in the potentiation of eNOS activation . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| The association of heat shock protein 90 ( Hsp 90 ) with endothelial nitric oxide synthase ( eNOS ) is a critical step in the mechanisms by which eNOS generates . ^^^ NO and O ( 2 ) , we hypothesized that Hsp 90 might also mediate eNOS dependent O ( 2 ) production . ^^^ In unstimulated 5 treated BCEC cultures low amounts of Hsp 90 were found to associate with eNOS . ^^^ Pretreatment with GA and / or increased the association of Hsp 90 with eNOS . ^^^ These data show that Hsp 90 is essential for eNOS dependent . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Recent studies showed that heat shock protein 90 ( HSP 90 ) enhances nitric oxide ( NO ) synthesis from endothelial and neuronal NO synthase ( eNOS and nNOS , respectively ) . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Using geldanamycin , an inhibitor of hsp 90 function , and overexpression of recombinant hsp 90 , we documented that the statin induced phosphorylation of eNOS on Ser 1177 was directly dependent on the ability of hsp 90 to recruit Akt in the eNOS complex . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Subsequently , other investigators demonstrated that eNOS interacts with heat shock protein 90 ( Hsp 90 ) following stimulation of endothelial cells with vascular endothelial growth factor ( VEGF ) , histamine , or fluid shear stress . ^^^ Therefore , we tested the hypotheses that ENAP 1 and Hsp 90 are the same protein and that BK activation of eNOS is dependent on Hsp 90 . ^^^ Coimmunoprecipitation of Hsp 90 with anti eNOS antibody reveals a Hsp 90 eNOS complex in endothelial cells under basal conditions that is increased following BK stimulation . ^^^ BK stimulated nitric oxide ( NO ) release is completely blocked by pretreatment with geldanamycin , a specific inhibitor of Hsp 90 , illustrating the importance of the Hsp 90 eNOS interaction . ^^^ In vitro binding assays with Hsp 90 glutathione S transferase fusion proteins show direct binding of eNOS with the middle domain ( residues 259 615 ) of Hsp90 . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| The binding of heat shock protein 90 ( HSP 90 ) to endothelial nitric oxide ( NO ) synthase ( eNOS ) can enhance eNOS activation . ^^^ The results show that GA can attenuate NO mediated dilation in human skin , suggesting a potential role for HSP 90 in activation of eNOS in the microcirculation . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Thus we examined whether heat shock protein 90 ( HSP 90 ) , phosphatidylinositol 3 kinase ( PI3K ) , and tyrosine kinase participate in ACh versus ADP induced eNOS activation in cerebral arterioles in vivo . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Hyperoxia did not alter eNOS association with Hsp 90 , nor did it modify nNOS or eNOS associations with calmodulin , the magnitude of eNOS tyrosine phosphorylation , or nNOS phosphorylation via calmodulin kinase . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In conclusion , we demonstrate that E 2 interaction with its receptor is followed by a vasorelaxant effect in rat aortic rings mediated by eNOS activation through both hsp 90 and akt / pkb dependent mechanisms . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Propranolol decreased NOS activity by 47 % and eNOS and Hsp 90 expression by 75 % and 72 % , respectively . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Western analysis revealed that both lipoproteins inhibited A 23187 stimulated association of heat shock protein 90 ( HSP 90 ) with eNOS without inhibiting phosphorylation of eNOS at serine 1179 ( phospho eNOS ) , an immunological index of electron flow through the enzyme . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Recently , heat shock protein 90 ( hsp 90 ) was shown to facilitate NO synthesis from eNOS and nNOS . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Heat shock protein 90 ( HSP 90 ) binds directly to eNOS , augmenting NO production . ^^^ We have used purified proteins to characterize further the mechanism by which HSP 90 increases eNOS activity at low ( 100 nm ) and high ( 10 microm ) Ca ( 2+ ) levels . ^^^ In the presence of calmodulin ( CaM ) , HSP 90 increased eNOS activity dose dependently at both low and high Ca ( 2+ ) concentrations . ^^^ The EC ( 50 ) values of eNOS for both Ca ( 2+ ) and CaM were decreased in the presence of HSP 90 . ^^^ HSP 90 also significantly increased the rate of NADPH dependent cytochrome c reduction by eNOS at both low and high Ca ( 2+ ) concentrations . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In LV tissue of SHR at 18 weeks , caveolin 1 and 3 were similarly decreased , but Hsp 90 upregulated , together with a downregulation of eNOS . ^^^ However , at 63 weeks , both eNOS and neuronal NOS ( nNOS ) were markedly upregulated in the LV of SHR , together with an upregulation of Hsp 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| We examined the influence of individual serine phosphorylation sites in endothelial nitric oxide synthase ( eNOS ) on basal and stimulated NO release , cooperative phosphorylation , and co association with hsp 90 and Akt . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Furthermore , statins may also increase eNOS activity via post translational activation of the phosphatidylinositol 3 kinase / protein kinase Akt ( PI 3 K / Akt ) pathway and / or through an interaction with the molecular chaperone heat shock protein 90 ( HSP 90 ) . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Endothelial nitric oxide ( NO ) synthase ( eNOS ) is regulated by heat shock protein 90 ( HSP 90 ) , a heat inducible protein ; however , the effect of heat shock on eNOS expression and eNO release is unknown . ^^^ We observed a 2 . 1 + / 0 . 1 fold increase in eNOS protein content , but no change in HSP 90 content , HSP 70 content , or HSP90 / eNOS association , 24 h after heat shock at 42 degrees C . ^^^ We also observed a 7 . 7 + / 1 . 5 fold increase in HSP 70 protein content , but did not observe a change in eNOS or HSP 90 24 h after heat shock at 45 degrees C . eNOS activity and maximal bradykinin stimulated NO release was significantly increased 24 h after heat shock at 42 degrees C . ^^^ Heat shock in rats ( core temperature : 42 degrees C , 15 min ) resulted in a significant increase in aortic eNOS , HSP 90 , and HSP 70 protein content . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In this study , we demonstrate that sGC exists in a complex with eNOS and heat shock protein 90 ( HSP 90 ) in aortic endothelial cells . ^^^ Formation of the sGC / eNOS / HSP90 complex is increased in response to eNOS activating agonists in a manner that depends on HSP 90 activity . ^^^ In vitro binding assays with glutathione S transferase fusion proteins that contain the alpha or beta subunit of sGC show that the sGC beta subunit interacts directly with HSP 90 and indirectly with eNOS . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Estrogen receptors ( ERalpha and ERbeta ) , heat shock proteins ( hsp 70 and hsp 90 ) , endothelial nitric oxide synthases ( eNOS ) , caveolin 1 , 2 and 3 and calmodulin were analyzed in total platelet lysate by immunoblotting . ^^^ Expression of ERalpha and ERbeta , hsp 70 , hsp 90 , eNOS , calmodulin , and caveolin 1 were observed in both sexes . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Synergistic activation of endothelial nitric oxide synthase ( eNOS ) by HSP 90 and Akt : calcium independent eNOS activation involves formation of an HSP 90 Akt CaM bound eNOS complex . ^^^ We recently used purified proteins to characterize the mechanisms by which heat shock protein 90 ( HSP 90 ) increases eNOS activity at low and high Ca2+ levels ( Takahashi , S . and Mendelsohn , M . ^^^ Here we extend these studies to explore interactions between HSP 90 , Akt , and eNOS . ^^^ In studies with purified proteins , HSP 90 increased the initial rate and maximal extent of Akt mediated eNOS phosphorylation and activation at low Ca2+ levels . ^^^ Akt was not observed in the eNOS complex in the absence of HSP 90 , but both active and inactive Akt associated with eNOS in the presence of HSP 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| T497A and T497A / S1179D eNOS generated 2 3 times more superoxide anion than WT eNOS , and both basal and stimulated interactions of T497A / S1179D eNOS with hsp 90 were reduced in co immunoprecipitation experiments . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Do we kNOw how HSP 90 and eNOS mediate lung injury in sickle cell disease . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| CsA treatment rapidly led to an increase in myocardial Hsp 90 expression promoting the recruitment of Akt and calcineurin , thereby promoting eNOS activation through Ser 1177 phosphorylation and Thr 495 dephosphorylation , respectively . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| An increase in the association of heat shock protein 90 ( HSP 90 ) with endothelial nitric oxide ( NO ) synthase ( eNOS ) is well recognized for increasing NO ( NO * ) production . ^^^ Despite the progress in this field , the mechanisms by which HSP 90 modulates eNOS remain unclear due , in part , to the fact that geldanamycin ( GA ) redox cycles to generate superoxide anion ( O ( 2 ) ( * ) and the fact that inhibiting HSP 90 with GA or radicicol ( RAD ) destabilizes tyrosine kinases that rely on the chaperone for maturation . ^^^ These data suggest that the tyrosine kinases , either directly or indirectly , and HSP 90 dependent signaling pathways act in concert to suppress uncoupled eNOS activity . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Ang 1 also led to stimulation of HSP 90 binding to eNOS and a significant increase in Akt phosphorylation . ^^^ Thirty minutes of pretreatment of cells with either 1 microg / ml geldanamycin ( a specific inhibitor of HSP 90 ) or 500 nM wortmannin [ a specific phosphatidylinositol 3 ( PI 3 ) kinase ( PI3K ) inhibitor ] significantly attenuated Ang 1 stimulated eNOS phosphorylation and NO production . ^^^ We conclude that stimulated HSP 90 binding to eNOS and activation of the PI 3 Akt pathway contribute to Ang 1 induced eNOS phosphorylation , NO production , and angiogenesis in PCAEC . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Regulation of endothelial NO synthase ( eNOS ) activity by fatty acid modifica tions , intracellular localization , interactions with heat shock protein 90 ( hsp 90 ) and caveolin , substrate and cofactor dependence , and phosphorylation might all affect the level of bioavailable NO . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Hypoxia increases Hsp 90 binding to eNOS via PI3K Akt in porcine coronary artery endothelium . ^^^ Hypoxia also led to a significant increase in Akt phosphorylation and upregulation of Hsp 90 binding to eNOS . ^^^ Pretreatment of cells with either 1 microg / ml geldanamycin ( a specific inhibitor of Hsp 90 ) or 500 nM wortmannin ( a specific PI 3 kinase inhibitor ) suppressed hypoxia stimulated Akt and eNOS phosphorylation and significantly attenuated hypoxia stimulated Hsp 90 binding to eNOS . ^^^ These data demonstrate that hypoxia leads to increased eNOS phosphorylation via stimulated Hsp 90 binding to eNOS and activation of the PI 3 Akt pathway . ^^^ We conclude that a coordinated interaction between Hsp 90 and PI 3 Akt may be an important mechanism by which eNOS activity and NO production is upregulated in hypoxic heart . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Immunoblots demonstrated that the eNOS caveolin interaction remained unaffected by vanadate , whereas vanadate promoted recruitment of the 90 kDa heat shock protein ( hsp 90 ) to eNOS . ^^^ We conclude that vanadate causes NO release via a mechanism that involves Akt induced eNOS phosphorylation and increased binding of the activator protein hsp 90 to eNOS . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVES : The interaction of the heat shock protein 90 ( Hsp 90 ) with the endothelial NO synthase ( eNOS ) has been shown to account for a sustained production of NO in vitro . ^^^ We further documented in vivo and in cultured endothelial cells that the cardioprotective effects of Hsp 90 were associated to its capacity to act as an adaptor for both the kinase Akt and the phosphatase calcineurin , thereby promoting eNOS serine 1177 phosphorylation and threonine 495 dephosphorylation , respectively . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Insulin resistance does not diminish eNOS expression , phosphorylation , or binding to HSP 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Like primary HUVEC cells , HUVEC CS express many of the key proteins necessary for vasodilator production , including epithelial nitric oxide synthase ( eNOS ) , HSP 90 , cav 1 and 2 , cPLA 2 , and COX 1 and 2 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Recently , it was demonstrated that eNOS activity is highly regulated by heat shock protein 90 ( HSP 90 ) . ^^^ We tested the hypothesis that adiponectin can prevent endothelial cell injury produced by angiotensin 2 through promotion of the association between eNOS and HSP 90 . ^^^ Western blotting and immunoprecipitation of the lysates from the treated cells showed that globular adiponectin could restore the association between eNOS and HSP 90 and enhance the phosphorylation of eNOS . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Immunoblots of eNOS , inducible NOS ( iNOS ) , and neuronal NOS ( nNOS ) in the immunoprecipitate of HSP 90 of heat shocked cells showed that there was a sevenfold increase in eNOS and no changes in iNOS and nNOS . ^^^ The results indicate that heat shock induced HSP 90 forms a complex with eNOS and activates it to increase NO concentration in the cardiac H9c2 cells . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In a concentration and time dependent manner , inhibition of Hsp 90 by 17 AAG decreased Akt and eNOS expression by 74 % and 81 % , respectively . ^^^ CONCLUSIONS : These findings indicate that Hsp 90 is important not only for Akt and eNOS phosphorylation but also for eNOS gene transcription and suggests that Hsp 90 may be a novel target for anti angiogenic therapy . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Inhibition of phosphatidylinositol 3 kinase or hsp 90 , pathways upstream of eNOS activation , also reduces carrageenan stimulated edema formation . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| OBJECTIVE : Induction of angiogenesis has been reported subsequent to eNOS overexpression or activation , the latter involving Hsp 90 as a chaperone protein . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Endothelial nitric oxide synthase ( eNOS ) , the major nitric oxide ( NO ) generating enzyme of the vasculature , is regulated through multiple interactions with proteins , including caveolin 1 , Hsp 90 , Ca2+ calmodulin , and the recently discovered eNOS interacting protein , NOSIP . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| The 90 kDa heat shock protein ( Hsp 90 ) plays an important role in endothelial nitric oxide synthase ( eNOS ) regulation . ^^^ Besides acting as an allosteric enhancer , Hsp 90 was shown to serve as a module recruiting Akt to phosphorylate the serine 1179 / 1177 ( bovine / human ) residue of eNOS . ^^^ Whether PDK 1 is involved in the actions of Hsp 90 on eNOS phosphorylation and function remains unknown . ^^^ To address this issue , we treated bovine eNOS stably transfected human embryonic kidney 293 cells with Hsp 90 inhibitors and determined the alterations of phospho eNOS , Akt , and PDK 1 . ^^^ Both geldanamycin and radicicol , two structurally different Hsp 90 inhibitors , selectively reduced serine 1179 phosphorylated eNOS , leading to decreased enzyme activity . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Geldanamycin ( 10 microg ml ( 1 ) ) , an agent known to inhibit heat shock protein 90 ( hsp 90 ) , reduced the level of ser 1177 eNOS in P + HR aortic segments . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| We measured the levels of eNOS by ELISA and its binding proteins including heat shock protein 90 ( Hsp 90 ) and caveolin 1 by Western blotting . ^^^ Neither Hsp 90 nor caveolin 1 important eNOS regulators appears to mediate the genotypesmoking effects on eNOS expression although HUVECs did produce more Hsp 90 when exposed to CSE . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Stimulated HSP 90 binding to eNOS and activation of the PI 3 Akt pathway contribute to globular adiponectin induced NO production : vasorelaxation in response to globular adiponectin . ^^^ Globular adiponectin induced eNOS phosphorylation was accompanied by eNOS HSP 90 Akt complex formation , resulting in a dose dependent increase in NO release . ^^^ Globular adiponectin stimulated binding of HSP 90 to eNOS , and inhibition of HSP 90 significantly suppressed globular adiponectin stimulated NO release . ^^^ These results indicate that stimulated HSP 90 binding to eNOS and activation of the PI 3 Akt pathway contribute to globular adiponectin induced eNOS phosphorylation and NO production , and to endothelium dependent vasorelaxation . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| In this work , we show by a variety of methods ( ozone chemiluminescence , biotin switch , and mass spectrometry ) that the molecular chaperone Hsp 90 is a target of S nitrosylation and identify a susceptible cysteine residue in the region of the C terminal domain that interacts with endothelial nitric oxide synthase ( eNOS ) . ^^^ Hsp 90 ATPase activity and its positive effect on eNOS activity are both inhibited by S nitrosylation . ^^^ Together , these data suggest that S nitrosylation may functionally regulate the general activities of Hsp 90 and provide a feedback mechanism for limiting eNOS activation . . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| BACKGROUND : Estradiol activates endothelial nitric oxide synthase ( eNOS ) by mechanisms that involve estrogen receptor alpha ( ERalpha ) , protein kinase B / Akt , mitogen activated protein kinases , and heat shock protein 90 ( HSP 90 ) . ^^^ However , inhibition of AMPK did not alter estradiol induced eNOS phosphorylation at serine 1177 or threonine 495 but decreased eNOS interaction with HSP 90 . ^^^ CONCLUSIONS : Taken together , these data indicate that AMPK activity is essential for estradiol induced eNOS activation via the promotion of eNOS interaction with HSP 90 . ^^^ |
|
| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Endothelial NO synthase ( eNOS ) activity is determined by heat shock protein 90 ( HSP 90 ) , caveolin 1 , and the cofactor tetrahydrobiopterin ( BH 4 ) . ^^^ Expression of eNOS , HSP 90 , caveolin 1 , Akt , phosphorylated eNOS ( eNOS Ser 1177 ) , and GTPCH 1 were determined by Western blot analysis . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Based on studies characterizing the interaction of G alpha 12 and the molecular chaperone Hsp 90 and the interaction of eNOS and Hsp 90 , the group proposed an interaction between G alpha 12 and eNOS and sought to determine the regulatory mechanisms , including the inferred dependence on Hsp 90 . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Multiple signaling inputs , including calcium , caveolin 1 , phosphorylation by several kinases , and binding to the 90 kDa heat shock protein ( Hsp 90 ) , regulate eNOS activity . ^^^ We demonstrate that in mammalian cells , the alpha subunit of heterotrimeric G 12 protein ( G alpha 12 ) can form a complex with eNOS in an activation and Hsp 90 independent manner . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Vascular soluble guanylate cyclase ( sGC ) exists in multimeric complexes with endothelial nitric oxide ( NO ) synthase ( eNOS ) and heat shock protein 90 ( hsp 90 ) . ^^^ Whereas disruption of hsp 90 eNOS complexes clearly attenuates eNOS dependent vascular relaxation , the contribution of sGC hsp 90 complexes to eNOS or NO donor dependent relaxations remains unclear . ^^^ These studies suggest that hsp 90 regulates both eNOS and sGC dependent relaxations . . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| We treated bovine pulmonary artery endothelial cells ( BPAECs ) with 20 HETE ( 1 microM ) or VEGF ( 8 . 3 nM ) and examined three molecular events known to activate eNOS : 1 ) phosphorylation at serine 1179 , 2 ) phosphorylation of protein kinase B ( Akt ) , which subsequently phosphorylates eNOS , and 3 ) association of eNOS with 90 kDa heat shock protein ( Hsp 90 ) . ^^^ VEGF had no effect on the binding of Hsp 90 with eNOS , whereas 20 HETE decreased the association of the protein partners . ^^^ Treatment with radicicol had no effect on 20 HETE induced relaxation of pulmonary arteries , consistent with an absence of effect on association of Hsp 90 to eNOS , whereas radicicol partially blocked VEGF evoked relaxations , possibly secondary to effects on endpoints other than Hsp 90 association with eNOS . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Tyrosine phosphorylation of eNOS and expression of calmodulin increased , but Hsp 90 decreased with all treatments and only raloxifene treatment increased caveolin 1 compared with OVX . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Tetrahydrobiopterin ( BH 4 ) and heat shock protein 90 ( hsp 90 ) have been anticipated to regulate endothelial nitric oxide synthase ( eNOS ) dependent superoxide anion radical ( O2 * ) generation in endothelial cells . ^^^ It is not known , however , whether hsp 90 and BH 4 increase O2 * in a synergistic manner , or whether this increase is a consequence of downstream changes in eNOS phosphorylation on serine 1179 ( eNOS S 1179 ) and changes in dimer / monomer distribution . ^^^ Here O2 * production from purified BH 4 free eNOS and eNOS : hsp 90 complexes determined by spin trapping methodology showed that hsp 90 neither inhibits O2 * nor alters the requirement of BH 4 to inhibit radical release from eNOS . ^^^ Radicicol , a hsp 90 inhibitor , disrupted eNOS : hsp 90 association , decreased eNOS S 1179 , but increased biopterin production in a dose dependent fashion . ^^^ These changes were followed by an increase in eNOS activity , demonstrating that high biopterin levels offset inhibition of eNOS phosphorylation and diminished interaction with hsp 90 . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| Rapid phosphorylation of ERK1 / 2 , protein kinase B / Akt , and eNOS serine 1177 by equol was paralleled by association of eNOS with heat shock protein 90 ( Hsp 90 ) and NO synthesis in human umbilical vein endothelial cells , expressing estrogen receptors ( ER ) alpha and ERbeta . ^^^ |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| NA |
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| Interacting proteins: P29474 and P07900 |
Pubmed |
SVM Score :0.0 |
| NA |
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