Norfuraneol dephosphorylates eNOS at threonine 495 and enhances eNOS activity in human endothelial cells

Abstract

NF enhances endothelial NO release most likely by promoting specific dephosphorylation of eNOS-Thr495 via PP1 in vitro and may be a promising compound to enhance endothelial function in vivo.

Toxic effects of xylazine on endothelial cells in combination with cocaine and 6-monoacetylmorphine

“…Cells were cultured to confluence on DMEM culture media (ATCC, Manassas, Virginia) with 10% fetal bovine serum (ATCC, Manassas, Virginia) [17, 18]. These cultures were maintained at 37 °C and 5% CO 2 [19].…”

Interplay of myosin phosphatase and protein phosphatase-2A in the regulation of endothelial nitric-oxide synthase phosphorylation and nitric oxide production

“…PKC and ROCK are the kinase candidates to target Thr497 under physiological conditions19, while the dephosphorylating phosphatase is not unambiguously identified. There appears to be a consensus in the literature that PP1 type phosphatase acts on phosphorylated Thr497 in eNOS (eNOS pThr497 ) in ECs101121. Surprisingly, the type of PP1 holoenzyme has not been identified yet, although this knowledge is essential to uncover physiological regulatory events in the dephosphorylation of eNOS pThr497 .…”

“…Several reports101121 have established that PP1 type enzyme dephosphorylates eNOS pThr497 , however, the mediatory role (direct or indirect) of PP2A or the CaM-dependent PP2B/calcineurin could not be excluded either15.…”

Citron Rho-interacting kinase mediates arsenite-induced decrease in endothelial nitric oxide synthase activity by increasing phosphorylation at threonine 497: Mechanism underlying arsenite-induced vascular dysfunction

“…In this regard, we recently reported that arsenite results in an acute decrease in NO production by increasing the phosphorylation of endothelial NO synthase (eNOS) at threonine 497 (eNOS-Thr 497 ; in bovine sequence) [10]. Furthermore, this increased eNOS-Thr 497 phosphorylation was shown to be mediated by the ROS/protein phosphatase 1 (PP1) signaling pathway, suggesting possible crosstalk between ROS and NO in arsenite-derived CVD development [10,11].…”

“…Several sites of phosphorylation, such as eNOS-Ser 1179 , eNOS-Thr 497 , and eNOS-Ser 116 , have been identified and evaluated [14,15]. Among those sites, phosphorylation of eNOS-Thr 497 decreases eNOS activity and NO production [11,15]. Although several kinases have been reported to mediate eNOS-Thr 497 phosphorylation, including AMP-activated protein kinase (AMPK) [16], protein kinase C (PKC) [17,18] and Rho-associated protein kinase (ROCK) [19,20], whether these kinases directly phosphorylate eNOS-Thr 497 has yet to be determined.…”